Effects of Taste Signaling Protein Abolishment on Gut Inflammation in an Inflammatory Bowel Disease Mouse Model

Inflammatory bowel disease (IBD) is one of the immune-related gastrointestinal disorders, including ulcerative colitis and Crohn's disease, that affects ...

Monell Chemical Senses Center

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&#x514D;&#x75AB;&#x7EC6;&#x80DE;&#x7684;&#x4EBA;&#x7C7B;&#x5916;&#x56F4;&#x54C1;&#x5473;&#x7CFB;&#x7EDF;&#xFF1A; &#x5360;&#x4E3B;&#x5BFC;&#x5730;&#x4F4D;&#x7684;&#x6811;&#x7A81;&#x72B6;&#x7EC6;&#x80DE;&#x548C; CD4 T &#x7EC6;&#x80DE;&#x3002;

Taste loss or alterations can seriously impact health and quality of life due to the resulting negative influence on eating habits and nutrition. Infection and inflammation are thought to be some of the most common causes of taste perception disorders. Supporting this view, neuro-immune interactions in the peripheral gustatory system have been identified, underlying the importance of this tissue in mucosal immunity, but we have little understanding of how these interactions influence taste perception directly or indirectly. This limited understanding is evident by the lack of even a basic knowledge of the resident immune cell populations in or near taste tissues. The present study characterized the distribution and population of the major immune cells and their subsets in healthy human anterior, lingual, fungiform papillae (FP) using immunohistochemistry. Dendritic cells (DCs) were the predominant innate immune cells in this tissue, including four subtypes: CD11c(+) DCs, DC-SIGN+ immature DCs, CD83(+) mature DCs, and CD1a(+) DCs (Langerhans cells). While most DCs were localized beneath the lamina propria and only moderately in the epithelium, CD1a(+) Langerhans cells were exclusively present within the epithelium and not in sub-strata. A small number of macrophages were observed. T lymphocytes were present throughout the FP with CD4(+) T cells more prevalent than CD8(+) T cells. Very few CD19(+) B lymphocytes were detected. The results show that DCs, macrophages, and T lymphocytes are the constitutive guardians of human FP taste tissue, with DCs and CD4 T cells being dominant, while B lymphocytes are rare under normal, healthy conditions. These observations provide a basic anatomical foundation for the immune response in the healthy human tongue as a basis for subsequent disease-related studies, but none of the present data indicate that the immune cell populations identified are, in fact, altered in individuals with abnormal taste perception.

Immune cells of the human peripheral taste system: dominant dendritic cells and CD4 T cells.

Perte de go&ucirc;t ou des alt&eacute;rations peuvent influer s&eacute;rieusement sant&eacute; et qualit&eacute; de vie en raison de l&#39;influence n&eacute;gative qui en r&eacute;sulte sur les habitudes alimentaires et la nutrition. Infection et l&#39;inflammation sont consid&eacute;r&eacute;s comme des causes plus fr&eacute;quentes des troubles de perception de go&ucirc;t. Soutenir cette vue, les interactions neuro-immunitaires dans le p&eacute;riph&eacute;rique syst&egrave;me gustatif ont &eacute;t&eacute; identifi&eacute;s, qui sous-tendent l&#39;importance de ce tissu dans l&#39;immunit&eacute; des muqueuses, mais nous avons peu de comprendre comment ces interactions influencent la perception gustative directement ou indirectement. Cette compr&eacute;hension limit&eacute;e est &eacute;vidente par le manque de m&ecirc;me une connaissance de base des populations r&eacute;sidentes de cellules immunitaires dans ou pr&egrave;s de tissus de go&ucirc;t. La pr&eacute;sente &eacute;tude caract&eacute;rise la distribution et la population des cellules immunitaires principaux et leurs sous-ensembles en sant&eacute; humaines ant&eacute;rieures, linguales, fongiformes papilles (FP) par immunohistochimie. Les cellules dendritiques (CD) sont les cellules immunitaires inn&eacute;es pr&eacute;dominants dans ce tissu, y compris quatre sous-types : DCs CD11c(+), DC-SIGN + DCs immatures, CD83(+) DCs matures et CD1a(+) DCs (cellules de Langerhans). Alors que la plupart DCs ont &eacute;t&eacute; localis&eacute;es sous la lamina propria et que mod&eacute;r&eacute;ment dans l&#39;&eacute;pith&eacute;lium, cellules de Langerhans CD1a(+) &eacute;taient exclusivement pr&eacute;sents dans l&#39;&eacute;pith&eacute;lium et pas dans le bassin. Un petit nombre de macrophages ont &eacute;t&eacute; observ&eacute;. Lymphocytes T &eacute;taient pr&eacute;sents tout au long de la FP avec les cellules T CD4 + plus pr&eacute;valente que les cellules T CD8. Les lymphocytes B CD19(+) tr&egrave;s peu ont &eacute;t&eacute; d&eacute;tect&eacute;s. Les r&eacute;sultats montrent que les DCs, les macrophages et les lymphocytes T sont les gardiens constitutives des tissus humains de go&ucirc;t FP, avec les contr&ocirc;leurs de domaine et de lymphocytes T CD4 des cellules &eacute;tant dominante, alors que les lymphocytes B sont rares dans des conditions normales et saines. Ces observations fournissent une base d&#39;anatomique fondamentale pour la r&eacute;ponse immunitaire dans la langue humaine saine comme base pour des &eacute;tudes ult&eacute;rieures li&eacute;e &agrave; la maladie, mais aucune de ces donn&eacute;es indiquent que les populations de cellules immunitaires identifi&eacute;es sont, en effet, chang&eacute;es chez les individus atteints de perception gustative anormale.

Les cellules immunitaires du syst&egrave;me p&eacute;riph&eacute;rique humains du go&ucirc;t : les cellules dendritiques dominantes et lymphocytes t CD4.

Geschmack Verlust oder Ver&auml;nderungen k&ouml;nnen ernsthaft Gesundheit und Lebensqualit&auml;t aufgrund der daraus resultierenden negativen Einfluss auf die Ern&auml;hrungsgewohnheiten und Ern&auml;hrung auswirken. Infektion und Entz&uuml;ndung werden gedacht, um einige der h&auml;ufigsten Ursachen von Geschmack Wahrnehmung St&ouml;rungen sein. Unterst&uuml;tzt diese Ansicht, Neuro-immunen Interaktionen im peripheren gustatorisches System identifiziert wurden, zugrunde liegt die Bedeutung dieses Gewebe in der Schleimhaut Immunit&auml;t, aber wir haben wenig Verst&auml;ndnis, wie diese Interaktionen Geschmack Wahrnehmung direkt oder indirekt beeinflussen. Dieses begrenzte Verst&auml;ndnis ist offensichtlich durch die mangelnde sogar grundlegende Kenntnisse der resident Immunzellen Bev&ouml;lkerungen im oder nahe dem Geschmack Gewebe. Die vorliegende Studie charakterisiert die Verteilung und die Bev&ouml;lkerung die wichtigsten Immunzellen und ihre Untergruppen im gesunden menschlichen anterior, lingual, fungiformen Papillen (FP) verwenden Immunohistochemistry. Dendritische Zellen (DCs) waren die vorherrschenden angeborenen immune Zellen in dieses Gewebe, einschlie&szlig;lich vier Untertypen: CD11c(+) DCs, DC-SIGN + unreife DCs, CD83(+) Reife DCs und DCs CD1a(+) (Langerhans-Zellen). W&auml;hrend die meisten DCs unterhalb der Lamina Propria und nur m&auml;&szlig;ig lokalisiert wurden in das Epithel CD1a(+) Langerhans-Zellen wurden ausschlie&szlig;lich innerhalb der Epithel und nicht in Sub-strata vorhanden. Eine kleine Anzahl von Makrophagen wurden beobachtet. T-Lymphozyten waren anwesend, w&auml;hrend die FP mit CD4(+) T-Zellen, die h&auml;ufiger als CD8(+) T-Zellen. Sehr wenige CD19(+) B-Lymphozyten gefunden. Die Ergebnisse zeigen, dass DCs, Makrophagen und T-Lymphozyten sind die konstitutiven W&auml;chter von menschlichem Gewebe der FP-Geschmack, mit DCs und CD4 T-Zellen, dominant, w&auml;hrend B-Lymphozyten selten unter normalen, gesunden Bedingungen sind. Diese Beobachtungen bieten eine grundlegende anatomische Grundlage f&uuml;r die Immunantwort in die gesunde menschliche Zunge als Grundlage f&uuml;r sp&auml;tere krankheitsbezogenen Untersuchungen, aber keine der vorliegenden Daten zeigen, dass die Immunzellen Bev&ouml;lkerung identifiziert tats&auml;chlich in den Einzelpersonen mit anormalen Geschmack Wahrnehmung ver&auml;ndert sind.

Immunzellen des menschlichen peripheren Geschmack Systems: dominante dendritische Zellen und CD4 T-Zellen.

Perdita di gusto o alterazioni possono influire seriamente salute e qualit&agrave; della vita a causa dell&#39;influenza negativa risultante su abitudini alimentari e nutrizione. Infezione e infiammazione sono pensati per essere alcune delle cause pi&ugrave; comuni di disturbi di percezione del gusto. Sostenere questa vista, neuro-immunitario interazioni nel sistema gustativo periferico sono stati identificati, sottostante l&#39;importanza di questo tessuto in immunit&agrave; mucosale, ma noi abbiamo poca comprensione di come queste interazioni influenzano la percezione gustativa direttamente o indirettamente. Questa comprensione limitata &egrave; evidente dalla mancanza di persino una conoscenza di base delle popolazioni delle cellule immunitarie residente in o vicino a tessuti di gusto. Lo studio presente ha caratterizzato la distribuzione e la popolazione delle principali cellule del sistema immunitario e loro sottoinsiemi di papille fungiformi, linguale e anteriore umani sani (FP) mediante immunoistochimica. Le cellule dendritiche (DCs) sono state le predominanti cellule immunitarie innate in questo tessuto, tra cui quattro sottotipi: CD11c(+) DCs, DC-segno + DCs immaturo e maturo DCs CD83(+) CD1a(+) DCs (cellule di Langerhans). Mentre la maggior parte dei controller di dominio erano localizzati sotto la lamina propria e solo moderatamente nell&#39;epitelio, cellule di Langerhans CD1a(+) erano esclusivamente presenti all&#39;interno dell&#39;epitelio e non in sub-strata. Un piccolo numero di macrofagi sono stato osservato. Linfociti T erano presenti in tutta la FP con cellule T CD4(+) pi&ugrave; diffuse rispetto a cellule cellule T. Sono stati rilevati molto pochi linfociti B CD19(+). I risultati mostrano che DCs, macrofagi e linfociti T sono i Guardiani costitutivi del tessuto umano di gusto FP, con DCs e T CD4 cellule essendo dominante, mentre i linfociti B sono rari in condizioni normali, sane. Queste osservazioni forniscono un fondamento base anatomico per la risposta immunitaria nella lingua umana sana come base per gli studi successivi riguardanti le malattie, ma nessuno dei presenti dati indicano che le popolazioni di cellule immunitarie identificate sono, infatti, alterate in individui con percezione gustativa anormale.

Le cellule immunitarie del sistema umano gusto periferici: dominante cellule dendritiche e cellule T CD4.

&#x5473;&#x306E;&#x640D;&#x5931;&#x307E;&#x305F;&#x306F;&#x5909;&#x66F4;&#x306B;&#x3064;&#x3044;&#x3066;&#x771F;&#x5263;&#x306B;&#x5065;&#x5EB7;&#x3068;&#x98DF;&#x751F;&#x6D3B;&#x3068;&#x6804;&#x990A;&#x306B;&#x95A2;&#x3059;&#x308B;&#x7D50;&#x679C;&#x306E;&#x8CA0;&#x306E;&#x5F71;&#x97FF;&#x306E;&#x305F;&#x3081;&#x306E;&#x751F;&#x6D3B;&#x306E;&#x8CEA;&#x306B;&#x5F71;&#x97FF;&#x3057;&#x307E;&#x3059;&#x3002;&#x611F;&#x67D3;&#x75C7;&#x3084;&#x708E;&#x75C7;&#x306F;&#x3001;&#x5473;&#x899A;&#x77E5;&#x899A;&#x969C;&#x5BB3;&#x306E;&#x6700;&#x3082;&#x4E00;&#x822C;&#x7684;&#x306A;&#x539F;&#x56E0;&#x306E;&#x4E00;&#x90E8;&#x304C;&#x3042;&#x308B;&#x3068;&#x8003;&#x3048;&#x3089;&#x308C;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x30D3;&#x30E5;&#x30FC;&#x3001;&#x795E;&#x7D4C;&#x514D;&#x75AB;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x652F;&#x63F4;&#x3001;&#x672B;&#x68A2;&#x306E;&#x5473;&#x899A;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x3067;&#x8B58;&#x5225;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x3001;&#x3053;&#x306E;&#x7D44;&#x7E54;&#x306E;&#x91CD;&#x8981;&#x6027;&#x306E;&#x7C98;&#x819C;&#x514D;&#x75AB;&#x3067;&#x3001;&#x57FA;&#x306B;&#x306A;&#x308B;&#x304C;&#x3001;&#x6211;&#x3005; &#x3069;&#x306E;&#x3088;&#x3046;&#x306B;&#x3053;&#x308C;&#x3089;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x306E;&#x5473;&#x77E5;&#x899A;&#x76F4;&#x63A5;&#x7684;&#x307E;&#x305F;&#x306F;&#x9593;&#x63A5;&#x7684;&#x306B;&#x5F71;&#x97FF;&#x3092;&#x4E0E;&#x3048;&#x308B;&#x5C0F;&#x3055;&#x306A;&#x7406;&#x89E3;&#x3092;&#x6301;&#x3063;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x9650;&#x3089;&#x308C;&#x305F;&#x7406;&#x89E3;&#x3082;&#x5E38;&#x99D0;&#x514D;&#x75AB;&#x7D30;&#x80DE;&#x7FA4;&#x3084;&#x5473;&#x7D44;&#x7E54;&#x8FD1;&#x304F;&#x306E;&#x57FA;&#x672C;&#x7684;&#x306A;&#x77E5;&#x8B58;&#x306E;&#x6B20;&#x5982;&#x306B;&#x3088;&#x3063;&#x3066;&#x660E;&#x767D;&#x3067;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x306E;&#x5206;&#x5E03;&#x3068;&#x4EBA;&#x53E3;&#x306E;&#x4E3B;&#x8981;&#x306A;&#x514D;&#x75AB;&#x7D30;&#x80DE;&#x3084;&#x514D;&#x75AB;&#x67D3;&#x8272;&#x3092;&#x7528;&#x3044;&#x305F;&#x305D;&#x306E;&#x30B5;&#x30D6;&#x30BB;&#x30C3;&#x30C8;&#x5065;&#x5EB7;&#x4EBA;&#x9593;&#x524D;&#x65B9;, &#x820C;, &#x8338;&#x72B6;&#x4E73;&#x982D; (FP) &#x3067;&#x7279;&#x5FB4;&#x3065;&#x3051;&#x3089;&#x308C;&#x307E;&#x3059;&#x3002;&#x6A39;&#x72B6;&#x7D30;&#x80DE; (Dc) &#x3055;&#x308C;&#x305F; 4 &#x3064;&#x306E;&#x30B5;&#x30D6;&#x30BF;&#x30A4;&#x30D7;&#x3092;&#x542B;&#x3080;&#x3053;&#x306E;&#x7D44;&#x7E54;&#x306E;&#x512A;&#x52E2;&#x306A;&#x751F;&#x5F97;&#x306E;&#x514D;&#x75AB;&#x7D30;&#x80DE;: CD11c(+) &#x306E; Dc&#x3001;DC-&#x8A18;&#x53F7; + &#x672A;&#x719F; DCs&#x3001;CD83(+) &#x6210;&#x719F;&#x3057;&#x305F; DCs &#x304A;&#x3088;&#x3073; CD1a(+) &#x306E; Dc &#xFF08;&#x30E9;&#x30F3;&#x30B2;&#x30EB;&#x30CF;&#x30F3;&#x30B9;&#x7D30;&#x80DE;&#xFF09;&#x3002;&#x307B;&#x3068;&#x3093;&#x3069; DCs &#x7C98;&#x819C;&#x4E0B;&#x3068;&#x3060;&#x3051;&#x3067;&#x9069;&#x5EA6;&#x306B;&#x5C40;&#x5728;&#x3057;&#x3066;&#x3044;&#x305F;&#x4E00;&#x65B9;&#x3001;&#x4E0A;&#x76AE;&#x306E; CD1a(+) &#x30E9;&#x30F3;&#x30B2;&#x30EB;&#x30CF;&#x30F3;&#x30B9;&#x7D30;&#x80DE;&#x4E0A;&#x76AE;&#x5185;&#x3068;&#x306E;&#x3066;&#x5C02;&#x3089;&#x5B58;&#x5728;&#x3057;&#x3066;&#x3044;&#x305F;&#x3002;&#x5C11;&#x6570;&#x306E;&#x30DE;&#x30AF;&#x30ED;&#x30D5;&#x30A1;&#x30FC;&#x30B8;&#x3092;&#x8A8D;&#x3081;&#x305F;.T &#x30EA;&#x30F3;&#x30D1;&#x7403;&#x3060;&#x308D;&#x3046;&#x3053;&#x306E; T &#x7D30;&#x80DE;&#x3088;&#x308A;&#x3082;&#x3082;&#x3063;&#x3068;&#x666E;&#x53CA;&#x3057;&#x3066; CD4(+) T &#x7D30;&#x80DE;&#x3068; FP &#x3092;&#x901A;&#x3057;&#x3066;&#x5B58;&#x5728;&#x3057;&#x3066;&#x3044;&#x305F;&#x3002;&#x975E;&#x5E38;&#x306B;&#x5C11;&#x6570;&#x306E; CD19(+) B &#x30EA;&#x30F3;&#x30D1;&#x7403;&#x304C;&#x691C;&#x51FA;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x305D;&#x306E;&#x7D50;&#x679C;&#x3092; Dc, &#x30DE;&#x30AF;&#x30ED;&#x30D5;&#x30A1;&#x30FC;&#x30B8;&#x304A;&#x3088;&#x3073;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x3072;&#x3068; FP &#x5473;&#x7D44;&#x7E54;&#x306E;&#x69CB;&#x6210;&#x5F0F;&#x306E;&#x4FDD;&#x8B77;&#x8005;&#x3067;&#x3042;&#x308B;&#x3001;DCs &#x3068; CD4 T &#x7D30;&#x80DE;&#x306E; B &#x30EA;&#x30F3;&#x30D1;&#x7403;&#x306F;&#x901A;&#x5E38;&#x3001;&#x5065;&#x5EB7;&#x306A;&#x6761;&#x4EF6;&#x306E;&#x4E0B;&#x3067;&#x73CD;&#x3057;&#x3044;&#x304C;&#x652F;&#x914D;&#x7684;&#x306A;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;. &#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x89B3;&#x6E2C;&#x57FA;&#x672C;&#x7684;&#x306A;&#x89E3;&#x5256;&#x5B66;&#x7684;&#x57FA;&#x76E4;&#x306E;&#x514D;&#x75AB;&#x5FDC;&#x7B54;&#x304C;&#x5065;&#x5168;&#x306A;&#x4EBA;&#x9593;&#x306E;&#x820C;&#x306B;&#x304A;&#x3051;&#x308B;&#x5F8C;&#x7D9A;&#x95A2;&#x9023;&#x306E;&#x75BE;&#x60A3;&#x7814;&#x7A76;&#x306E;&#x305F;&#x3081;&#x306E;&#x57FA;&#x790E;&#x3068;&#x3057;&#x3066;&#x3092;&#x63D0;&#x4F9B;&#x304C;&#x3069;&#x308C;&#x3082;&#x73FE;&#x5728;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306E;&#x8B58;&#x5225;&#x514D;&#x75AB;&#x7D30;&#x80DE;&#x96C6;&#x56E3;&#x306F;&#x3001;&#x5B9F;&#x969B;&#x306B;&#x306F;&#x3001;&#x7570;&#x5E38;&#x306A;&#x5473;&#x899A;&#x3092;&#x6301;&#x3064;&#x500B;&#x4EBA;&#x3067;&#x5909;&#x66F4;&#x3055;&#x308C;&#x307E;&#x3059;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;

&#x3072;&#x3068;&#x672B;&#x68A2;&#x5473;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x306E;&#x514D;&#x75AB;&#x7D30;&#x80DE;: &#x652F;&#x914D;&#x7684;&#x306A;&#x6A39;&#x72B6;&#x7D30;&#x80DE;&#x304A;&#x3088;&#x3073; CD4 T &#x7D30;&#x80DE;&#x3002;

&#xB9DB; &#xC190;&#xC2E4;&#xC774; &#xB098; &#xBCC0;&#xACBD; &#xAC74;&#xAC15;&#xACFC; &#xC2DD;&#xC2B5;&#xAD00;&#xACFC; &#xC601;&#xC591;&#xC5D0; &#xACB0;&#xACFC; &#xBD80;&#xC815;&#xC801;&#xC778; &#xC601;&#xD5A5;&#xC73C;&#xB85C; &#xC778;&#xD574; &#xC0B6;&#xC758; &#xC9C8; &#xC601;&#xD5A5; &#xC2EC;&#xAC01; &#xD558; &#xAC8C; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xAC10;&#xC5FC;&#xACFC; &#xC5FC;&#xC99D;&#xC774; &#xB9DB; &#xC9C0; &#xAC01; &#xC7A5;&#xC560;&#xC758; &#xAC00;&#xC7A5; &#xC77C;&#xBC18;&#xC801;&#xC778; &#xC6D0;&#xC778; &#xC911; &#xC77C;&#xBD80; &#xAC83;&#xC73C;&#xB85C; &#xC0DD;&#xAC01; &#xB429;&#xB2C8;&#xB2E4;. &#xC8FC;&#xBCC0; &#xBBF8;&#xAC01; &#xC2DC;&#xC2A4;&#xD15C;&#xC5D0;&#xC774; &#xBDF0;, &#xC2E0;&#xACBD;-&#xBA74;&#xC5ED; &#xC791;&#xC6A9;&#xC744; &#xC9C0; &#xC6D0;&#xD558;&#xB294; &#xD655;&#xC778; &#xD55C; &#xC810; &#xB9C9; &#xBA74;&#xC5ED;&#xC774; &#xC870;&#xC9C1;&#xC758; &#xC911;&#xC694;&#xC131;&#xC744; &#xAE30;&#xBCF8; &#xD558;&#xC9C0;&#xB9CC; &#xC6B0;&#xB9AC;&#xB294; &#xC880; &#xC774;&#xD574;&#xB97C; &#xC9C1;&#xC811;&#xC801;&#xC73C;&#xB85C; &#xB610;&#xB294; &#xAC04;&#xC811;&#xC801;&#xC73C;&#xB85C; &#xC774;&#xB7EC;&#xD55C; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC758; &#xB9DB; &#xC9C0; &#xAC01;&#xC5D0; &#xC601;&#xD5A5;&#xC744;. &#xC774; &#xC81C;&#xD55C; &#xB41C; &#xC774;&#xD574; &#xB610;&#xB294; &#xB9DB; &#xC870;&#xC9C1; &#xC778;&#xADFC; &#xC8FC;&#xBBFC; &#xBA74;&#xC5ED; &#xC138;&#xD3EC; &#xC778;&#xAD6C;&#xB3C4; &#xAE30;&#xBCF8;&#xC801;&#xC778; &#xC9C0;&#xC2DD;&#xC758; &#xBD80;&#xC871;&#xC5D0; &#xC758;&#xD574; &#xBD84;&#xBA85; &#xD558;&#xB2E4;. &#xD604;&#xC7AC;&#xC758; &#xC5F0;&#xAD6C; &#xD2B9;&#xC9D5; &#xBD84;&#xD3EC; &#xBC0F; &#xC778;&#xAD6C; &#xC8FC;&#xC694; &#xBA74;&#xC5ED; &#xC138;&#xD3EC;&#xC640; &#xAE30;&#xC220;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xAC74;&#xAC15; &#xD55C; &#xC778;&#xAC04;&#xC758; &#xC55E;&#xCABD;&#xC5D0;, &#xC5B8;&#xC5B4;&#xC801;, fungiform papillae (FP)&#xC5D0; &#xADF8;&#xB4E4;&#xC758; &#xD558;&#xC704; &#xC9D1;&#xD569;&#xC785;&#xB2C8;&#xB2E4;. &#xC218;&#xC9C0;&#xC0C1; &#xC138;&#xD3EC; (DCs)&#xC740; 4 &#xAC1C;&#xC758; &#xD558;&#xC704; &#xC720;&#xD615; &#xB4F1;&#xC774; &#xC870;&#xC9C1;&#xC5D0; &#xC8FC;&#xB41C; &#xD0C0;&#xACE0; &#xB09C; &#xBA74;&#xC5ED; &#xC138;&#xD3EC;: CD11c(+) Dc, DC-&#xAE30;&#xD638; + &#xBBF8; &#xC219; DCs, CD83(+) &#xC131;&#xC219; DCs &#xBC0F; CD1a(+) Dc (Langerhans &#xC138;&#xD3EC;). &#xB300;&#xBD80;&#xBD84;&#xC758; DCs lamina propria &#xC544;&#xB798;&#xC640; &#xC801;&#xB2F9;&#xD788;&#xB9CC; &#xD604;&#xC9C0; &#xD588;&#xB2E4; &#xD558;&#xB294; &#xB3D9;&#xC548; CD1a(+) Langerhans &#xC138;&#xD3EC;&#xB294; &#xC0C1;&#xD53C;&#xC758; &#xC0C1;&#xD53C; &#xB0B4; sub-strata&#xC5D0;&#xC11C; &#xD558;&#xC9C0; &#xB3C5;&#xC810;&#xC801;&#xC73C;&#xB85C; &#xCC38;&#xC11D; &#xD588;&#xB2E4;. &#xB300; &#xC2DD; &#xC138;&#xD3EC; &#xC218;&#xAC00; &#xC801;&#xC740; &#xAD00;&#xCC30; &#xD588;&#xB2E4;. T &#xB9BC;&#xD504; &#xD1A8; CD8(+) T &#xC138;&#xD3EC; &#xBCF4;&#xB2E4; &#xB354; &#xB110;&#xB9AC; CD4(+) T &#xC138;&#xD3EC;&#xC640; FP&#xB97C; &#xD1B5;&#xD574; &#xCC38;&#xC11D; &#xD588;&#xB2E4;. &#xAC70;&#xC758; CD19(+) B &#xC138;&#xD3EC; &#xBC1C;&#xACAC; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xACB0;&#xACFC; &#xD45C;&#xC2DC; Dc&#xC640; &#xB300; &#xC2DD; &#xC138;&#xD3EC;, T &#xC138;&#xD3EC;&#xB294; &#xC778;&#xAC04;&#xC758; FP &#xB9DB; &#xC870;&#xC9C1;&#xC758; &#xC81C;&#xC815; &#xC218;&#xD638;&#xC790;, Dcs&#xC640; CD4 T &#xC138;&#xD3EC; B &#xC138;&#xD3EC;&#xB294; &#xC815;&#xC0C1;&#xC801;&#xC774; &#xACE0; &#xAC74;&#xAC15; &#xD55C; &#xC870;&#xAC74;&#xC5D0;&#xC11C; &#xB4DC;&#xBB38; &#xC9C0;&#xBC30;, &#xB418; &#xACE0;. &#xC774;&#xB7EC;&#xD55C; &#xAD00;&#xCE21; &#xC774;&#xD6C4; &#xC9C8;&#xBCD1; &#xAD00;&#xB828; &#xC5F0;&#xAD6C;&#xC5D0; &#xB300; &#xD55C; &#xAE30;&#xC900;&#xC73C;&#xB85C; &#xAC74;&#xAC15; &#xD55C; &#xC778;&#xAC04;&#xC758; &#xD600;&#xC5D0; &#xBA74;&#xC5ED; &#xBC18;&#xC751;&#xC5D0; &#xB300; &#xD55C; &#xAE30;&#xBCF8;&#xC801;&#xC778; &#xD574;&#xBD80;&#xD559; &#xC801; &#xAE30;&#xCD08;&#xB97C; &#xC81C;&#xACF5; &#xD558;&#xC9C0;&#xB9CC; &#xB370;&#xC774;&#xD130; &#xD45C;&#xC2DC; &#xC911; &#xBE44;&#xC815;&#xC0C1;&#xC801;&#xC778; &#xB9DB; &#xC9C0; &#xAC01;&#xACFC; &#xAC1C;&#xC778; &#xC2DD;&#xBCC4; &#xBA74;&#xC5ED; &#xC138;&#xD3EC; &#xC778;&#xAD6C; &#xBCC0;&#xACBD; &#xC0AC;&#xC2E4;, &#xB098;&#xD0C0;&#xB0C5;&#xB2C8;&#xB2E4;.

&#xC778;&#xAC04;&#xC758; &#xC8FC;&#xBCC0; &#xB9DB; &#xC2DC;&#xC2A4;&#xD15C;&#xC758; &#xBA74;&#xC5ED; &#xC138;&#xD3EC;: &#xC9C0;&#xBC30;&#xC801;&#xC778; &#xC218;&#xC9C0;&#xC0C1; &#xC138;&#xD3EC;&#xC640; CD4 T &#xC138;&#xD3EC;.

P&eacute;rdida de gusto o alteraciones seriamente pueden afectar la salud y calidad de vida debido a la influencia negativa que resulta en h&aacute;bitos alimentarios y nutrici&oacute;n. Infecci&oacute;n y la inflamaci&oacute;n se cree que algunas de las causas m&aacute;s comunes de trastornos de la percepci&oacute;n del gusto. Apoyando esta opini&oacute;n, interacciones neuro-inmune en el sistema gustativo perif&eacute;rico han sido identificados, subyace la importancia de este tejido en Inmunidad mucosal, pero tenemos poca comprensi&oacute;n de c&oacute;mo estas interacciones influir en la percepci&oacute;n del gusto directamente o indirectamente. Esta comprensi&oacute;n limitada es evidente por la falta de incluso un conocimiento b&aacute;sico de las poblaciones de c&eacute;lulas inmunitarias residente en o cerca de los tejidos de gusto. El presente estudio caracteriza la distribuci&oacute;n y la poblaci&oacute;n de las principales c&eacute;lulas inmunes y sus subconjuntos en saludables papilas humanas anteriores, linguales, fungiformes (FP) mediante inmunohistoqu&iacute;mica. Las c&eacute;lulas dendr&iacute;ticas (DCs) fueron las c&eacute;lulas inmunitarias innatas predominantes en este tejido, incluyendo cuatro subtipos: DCs CD11c(+), DC-SIGN + inmaduros DCs DCs maduros CD83(+) y DCs CD1a(+) (c&eacute;lulas de Langerhans). Mientras que la mayor&iacute;a DCs fueron localizados debajo de la l&aacute;mina propia y s&oacute;lo moderadamente en el epitelio, las c&eacute;lulas de Langerhans CD1a(+) estaban exclusivamente presentes dentro del epitelio y no en sub-strata. Se observ&oacute; una peque&ntilde;a cantidad de macr&oacute;fagos. Los linfocitos T estuvieron presentes a lo largo de la FP con las c&eacute;lulas de T de CD4 m&aacute;s frecuentes que las c&eacute;lulas T CD8. Se detectaron muy pocos linfocitos B CD19(+). Los resultados muestran que DCs, macr&oacute;fagos y linfocitos T son los guardianes constitutivos de tejido humano de gusto FP, con DCs y T CD4 c&eacute;lulas siendo dominante, mientras que los linfocitos B son raros en condiciones normales y saludables. Estas observaciones proporcionan una base anat&oacute;mica b&aacute;sica para la respuesta inmune en la lengua humana sana como base para posteriores estudios relacionados con la enfermedad, pero ninguno de los datos actuales indican que las poblaciones de c&eacute;lulas inmunitarias identificadas son, de hecho, alteradas en individuos con la percepci&oacute;n del gusto anormal.

Las c&eacute;lulas inmunes del sistema humano gusto perif&eacute;rica: dominantes c&eacute;lulas dendr&iacute;ticas y linfocitos T CD4.

The impact of chronic rhinosinusitis (CRS) on the olfactory mucosa (OM) is dramatic. Cellular profiles and epithelial integrity in OM biopsies were evaluated using histological and immunohistochemical methods to define a strategy for future histological studies of CRS. We have examined nasal biopsies of 54 CRS patients (18-63 years old) and have defined specific histopathological patterns of the OM: normal pseudostratified, goblet cell hyperplasia, squamous metaplasia, and erosion. Goblet cell hyperplasia was most similar to a normal pseudostratified OM pattern but with goblet cells intermixed in the apical layers. Squamous metaplasia exhibited an absence of olfactory supporting cells and had olfactory sensory neurons that were morphologically abnormal. It is unknown if these neurons would be functional in this type of tissue transformation. The pattern of erosion exhibited a severe loss of epithelial layers and a higher prevalence of infiltrating inflammatory cells within the olfactory epithelium when compared to the other OM patterns. Although it is not known if the OM patterns we have noted correspond to specific stages or distinct pathways of the disease, the template proposed here can be used in further studies to understand how the histopathological progression of CRS relates to olfactory loss and the response to treatment.

Analysis of the olfactory mucosa in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a complex heterogeneous inflammatory disease that affects the nasal cavity, but the pathological examination of the olfactory mucosa (OM) in this disease has been limited.

Neuropathology of the olfactory mucosa in chronic  rhinosinusitis.

&#x5065;&#x5EB7;&#x7684;&#x5473;&#x89C9;&#x7CFB;&#x7EDF;&#x662F;&#x91CD;&#x8981;&#x7684;&#x8425;&#x517B;&#x548C;&#x6574;&#x4F53;&#x751F;&#x6D3B;&#x8D28;&#x91CF;&#x3001; &#x7EF4;&#x62A4;&#x548C;&#x5473;&#x89C9;&#x969C;&#x788D;&#x662F;&#x4E0E;&#x8BB8;&#x591A;&#x708E;&#x75C7;&#x56FD;&#x5BB6;&#x76F8;&#x5173;&#x8054;&#x3002;&#x6211;&#x4EEC;&#x5148;&#x524D;&#x786E;&#x5B9A;&#x7684;&#x514D;&#x75AB;&#x7EC6;&#x80DE;&#x5728;&#x6B63;&#x5E38;&#x4EBA;&#x7684;&#x5473;&#x89C9;&#x7EC4;&#x7EC7; &#xFF1B;&#x4ED6;&#x4EEC;&#x662F;&#x4E3B;&#x8981;&#x662F;&#x6811;&#x7A81;&#x72B6;&#x7EC6;&#x80DE;&#x548C; CD4 T &#x7EC6;&#x80DE;&#x4E0E;&#x5C11;&#x91CF;&#x5DE8;&#x566C;&#x7EC6;&#x80DE;&#x548C; B &#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x672C;&#x3002;&#x7136;&#x800C;&#xFF0C;&#x6709;&#x5C11;&#x6570;&#x62A5;&#x544A;&#x5404;&#x4E9A;&#x578B;&#x7684;&#x9A7B;&#x5730;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x4E2D;&#x6216;&#x5176;&#x9644;&#x8FD1;&#x5473;&#x9053;&#x7EC4;&#x7EC7;&#x3002;&#x672C;&#x7814;&#x7A76;&#x8FDB;&#x4E00;&#x6B65;&#x4E3A;&#x7279;&#x70B9;&#x7684;&#x5206;&#x5E03;&#x548C;&#x4EBA;&#x53E3;&#x7684; T &#x7EC6;&#x80DE;&#x539F;&#x4F4D;&#x6D3B;&#x68C0;&#x7684;&#x5065;&#x5EB7;&#x4EBA;&#x7C7B;&#x83CC;&#x72B6;&#x4E73;&#x5934; (FP) &#x5185;&#x4E3B;&#x8981;&#x7684;&#x4E9A;&#x578B;&#x3002;&#x514D;&#x75AB;&#x7EC4;&#x7EC7;&#x5316;&#x5B66;&#x5206;&#x6790;&#x8868;&#x660E; (Th) 1 T &#x8F85;&#x52A9;&#x7EC6;&#x80DE; &#xFF08;CCR5 +) &#x662F;&#x5728; FP Th2 T &#x7EC6;&#x80DE; (CCR4 +) &#x6BD4;&#x4EFB;&#x4F55;&#x65F6;&#x5019;&#x90FD;&#x66F4;&#x52A0;&#x7A81;&#x51FA;&#x3002;CD45RO + &#x8BB0;&#x5FC6; T &#x7EC6;&#x80DE;&#x662F;&#x4E3B;&#x8981;&#x7684; T &#x7EC6;&#x80DE;&#x5473;&#x89C9;&#x7684;&#x7EC4;&#x7EC7;&#xFF0C;&#x800C; CD45RA + &#x5929;&#x771F; T &#x7EC6;&#x80DE;&#x5219;&#x5C11;&#x89C1;&#x3002;&#x5173;&#x4E8E;&#x7EC4;&#x7EC7;&#x7684; subcompartments&#xFF0C;&#x6700;&#x4E0A;&#x76AE;&#x5185;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x662F; fps &#x7684; &gamma; / &#x4E09;&#x89D2;&#x6D32; T &#x7EC6;&#x80DE;&#xFF0C;&#x800C;&#x56FA;&#x6709;&#x5C42;&#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x7684;&#x4E3B;&#x8981;&#x5B50;&#x7C7B;&#x578B;&#x662F; fps &#x7684; &alpha;/&beta; T &#x7EC6;&#x80DE;&#x3002;&#x89C4;&#x7BA1; T &#x7EC6;&#x80DE;&#xFF0C;&#x5FEB;&#x9012; CTLA 4 (CD152) &#x548C;&#x767D;&#x7EC6;&#x80DE;&#x4ECB;&#x7D20;-2 &#x53D7;&#x4F53; &#xFF08;IL 2R&#x3001; CD25&#xFF09; &#x53D1;&#x73B0;&#x5728;&#x4F4E;&#x6C34;&#x5E73;&#x7684; FP&#x3002;T &#x7EC6;&#x80DE;&#x968F;&#x65F6;&#x51C6;&#x5907;&#x54CD;&#x5E94;&#x708E;&#x75C7;&#x548C;&#x611F;&#x67D3;&#x6027;&#x4FAE;&#x8FB1;&#xFF0C;&#x5E76;&#x53EF;&#x80FD;&#x5728;&#x6025;&#x6027;&#x548C;&#x6162;&#x6027;&#x708E;&#x75C7;&#x72B6;&#x6001;&#x671F;&#x95F4;&#x89C2;&#x5BDF;&#x5230;&#x7684;&#x5473;&#x9053;&#x6539;&#x5EFA;&#x5DE5;&#x7A0B;&#x4E2D;&#x53D1;&#x6325;&#x4F5C;&#x7528;&#x3002;

&#x5916;&#x56F4;&#x54C1;&#x5473;&#x7EC4;&#x7EC7;&#x7684;&#x5065;&#x5EB7;&#x4EBA;&#x7C7B;&#x6210;&#x4EBA; T &#x7EC6;&#x80DE;&#xFF1A; &#x4E3B;&#x8981;&#x8BB0;&#x5FC6; T &#x7EC6;&#x80DE;&#x548C; Th-1 &#x7684;&#x5355;&#x5143;&#x683C;&#x3002;

A healthy taste system is important to the maintenance of nutrition and overall quality of life, and taste disorders are associated with many inflammatory states. We previously determined the immune cells in normal human gustatory tissue; they are predominantly dendritic cells and CD4 T cells with a few macrophages and B lymphocytes present. There are, however, few reports of the subtypes of resident lymphocytes in or near taste tissues. The present study further characterized the distribution and population of the major subtypes of T cells in situ within biopsies of healthy human fungiform papillae (FP). Immunohistochemical analyses indicated that T-helper (Th)1 cells (CCR5+) were more predominant in FP than Th2 T cells (CCR4+). CD45RO+ memory T cells were the principal T cells in gustatory tissue, whereas CD45RA+ naive T cells were uncommon. Regarding subcompartments of the tissue, most intraepithelial lymphocytes of FPs were gamma/delta T cells, whereas the major subtype of lymphocytes in the lamina propria were alpha/beta T cells. Regulatory T cells that express CTLA-4 (CD152) and interleukin-2 receptors (IL-2R, CD25) were found at low levels in FP. The T cells stand ready to respond to inflammatory and infectious insults and may play a role in the taste alterations observed during acute and chronic inflammatory states.

The T cells in peripheral taste tissue of healthy human adults: predominant memory T cells and Th-1 cells.

Un syst&egrave;me de go&ucirc;t sain est important pour le maintien de la nutrition et de la qualit&eacute; de vie globale, et troubles du go&ucirc;t sont associ&eacute;s &agrave; de nombreux &Eacute;tats inflammatoires. Nous avons d&eacute;termin&eacute; pr&eacute;c&eacute;demment les cellules immunitaires dans les tissus normaux de gustatif humaine ; ils sont des cellules dendritiques principalement et cellules CD4 T avec quelques des macrophages et des lymphocytes B actuels. Cependant, il y a peu de rapports des sous-types de lymphocytes r&eacute;sidant dans ou pr&egrave;s des tissus de go&ucirc;t. La pr&eacute;sente &eacute;tude caract&eacute;rise davantage la distribution et la population des principaux sous-types de cellules T in situs dans les biopsies de la papilles fongiformes humaine saine (FP). L&#39;analyse immunohistochimique indique que les cellules T-helper (Th) 1 (CCR5 +) &eacute;taient plus pr&eacute;dominants dans la FP que les cellules Th2 T (CCR4 +). CD45RO + cellules T m&eacute;moires &eacute;taient les principales cellules de T dans les tissus gustatifs, tandis que na&iuml;ve T cellules CD45RA + &eacute;taient rares. Concernant sous-compartiments du tissu, plus des lymphocytes intra-&eacute;pith&eacute;liaux de FPs &eacute;taient cellules gamma/delta T, tandis que le sous-type majeur des lymphocytes dans la lamina propria &eacute;taient lymphocytes T alpha/b&ecirc;ta. T r&eacute;gulateurs cellules qu&#39;express CTLA-4 (CD152) et les r&eacute;cepteurs de l&#39;interleukine 2 (IL-2R, CD25) ont &eacute;t&eacute; trouv&eacute;s &agrave; des niveaux faibles dans la FP. Les cellules T sont pr&ecirc;ts &agrave; r&eacute;pondre aux insultes inflammatoires et infectieuses et peuvent jouer un r&ocirc;le dans les alt&eacute;rations de go&ucirc;t observ&eacute;es au cours des &Eacute;tats inflammatoires aigu&euml;s et chroniques.

Les cellules T dans les tissus p&eacute;riph&eacute;riques go&ucirc;t des adultes en bonne sant&eacute; humaines : cellules de T de m&eacute;moires pr&eacute;dominantes et Th-1.

Ein gesunder Geschmack-System ist wichtig f&uuml;r die Aufrechterhaltung der Ern&auml;hrung und Lebensqualit&auml;t insgesamt, und Geschmack Erkrankungen viele entz&uuml;ndliche Zust&auml;nde zugeordnet sind. Wir werden vorher festgelegte die Immunzellen im normalen menschlichen gustatorisches Gewebe; Sie sind &uuml;berwiegend dendritische Zellen und CD4 T-Zellen mit wenigen Makrophagen und B-Lymphozyten vorhanden. Jedoch gibt es einige Berichte der Subtypen von resident Lymphozyten im oder nahe dem Geschmack Gewebe. Die vorliegende Studie weiter charakterisiert, die Verteilung und die Bev&ouml;lkerung der gro&szlig;en Subtypen von T-Zellen, die in-situ in Biopsien der gesunden menschlichen fungiformen Papillen (FP). Immunhistochemische Analysen darauf hingewiesen, dass T-Helfer (Th) 1 (CCR5 +) Zellen wurden mehr vorherrschende in FP als Th2-T-Zellen (CCR4 +). CD45Ro + T Speicherzellen waren die wichtigsten T-Zellen im gustatorisches Gewebe, w&auml;hrend CD45RA + naiven T-Zellen ungew&ouml;hnlich waren. Bez&uuml;glich Subcompartments des Gewebes waren die meisten intraepitheliale Lymphozyten fps Gamma/Delta T-Zellen, w&auml;hrend der gro&szlig;e Untertyp von Lymphozyten in der Lamina Propria waren Alpha/Beta-T-Zellen. Regulatorische T-Zellen, dass ausdr&uuml;ckliche CTLA-4 (CD152) und Interleukin-2-Rezeptoren (IL-2R, CD25) fanden sich auf niedrigem Niveau in FP. Die T-Zellen stehen bereit, um entz&uuml;ndliche und infekti&ouml;se Beleidigungen reagieren und k&ouml;nnen eine Rolle in dem Geschmack-Umbau w&auml;hrend akuten und chronischen entz&uuml;ndlichen Zust&auml;nden beobachtet.

Die T-Zellen im peripheren Geschmack Gewebe des gesunden menschlichen Erwachsenen: vorherrschende T Ged&auml;chtniszellen und der Th-1.

Un sistema sano gusto &egrave; importante per il mantenimento della nutrizione e della qualit&agrave; complessiva della vita, e disturbi del gusto sono associati con molti Stati infiammatori. In precedenza abbiamo determinato le cellule immunitarie nel tessuto gustativo umano normale; Essi sono prevalentemente dendritiche e le cellule T CD4 con un paio di macrofagi e linfociti B presenti. Ci sono, tuttavia, alcuni rapporti dei sottotipi di linfociti residente in o vicino a tessuti di gusto. Lo studio presente ha caratterizzato ulteriormente la distribuzione e la popolazione dei sottotipi principali di cellule T in situ all&#39;interno di biopsie di papille fungiformi umani sani (FP). Analisi immunoistochimica indicano che le cellule T-helper (Th) 1 (CCR5 +) erano pi&ugrave; predominante in FP di cellule Th2 T (CCR4 +). Cellule memoria T CD45RO + erano le principali cellule T in tessuto gustativo, mentre CD45RA + cellule T naive sono stati rare. Per quanto riguarda subcompartments del tessuto, pi&ugrave; linfociti intraepiteliali di FPs erano cellule T gamma/delta, mentre il principale sottotipo di linfociti nella lamina propria erano cellule T alfa/beta. T regolatorie cellule che esprimere CTLA-4 (CD152) e recettori interleuchina-2 (IL-2R, CD25) sono stati trovati a livelli bassi in FP. Le cellule T stanno pronte a rispondere agli insulti infiammatori e infettivi e possono giocare un ruolo nelle alterazioni di gusto osservate durante gli Stati infiammatori acuti e cronici.

Le cellule T nel tessuto periferico gusto di adulti sani umani: memoria predominante T e cellule Th-1.

&#x5065;&#x5EB7;&#x5473;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x304C;&#x6804;&#x990A;&#x3068;&#x751F;&#x6D3B;&#x306E;&#x5168;&#x4F53;&#x7684;&#x306A;&#x306E;&#x8CEA;&#x306E;&#x7DAD;&#x6301;&#x306B;&#x91CD;&#x8981;&#x3067;&#x3042;&#x308B;&#x3057;&#x3001;&#x5473;&#x899A;&#x969C;&#x5BB3;&#x306F;&#x591A;&#x304F;&#x306E;&#x708E;&#x75C7;&#x72B6;&#x614B;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x6211;&#x3005; &#x306F;&#x4EE5;&#x524D;&#x3001;&#x901A;&#x5E38;&#x306E;&#x4EBA;&#x9593;&#x306E;&#x5473;&#x899A;&#x7D44;&#x7E54;&#x514D;&#x75AB;&#x7D30;&#x80DE;&#x3092;&#x6C7A;&#x5B9A;;&#x5F7C;&#x3089;&#x306F;&#x4E3B;&#x306B;&#x6A39;&#x72B6;&#x7D30;&#x80DE;&#x304A;&#x3088;&#x3073; cd4 &#x967D;&#x6027; T &#x7D30;&#x80DE;&#x6570;&#x306E;&#x30DE;&#x30AF;&#x30ED;&#x30D5;&#x30A1;&#x30FC;&#x30B8;&#x3068; B &#x30EA;&#x30F3;&#x30D1;&#x7403;&#x306E;&#x5B58;&#x5728;&#x3067;&#x3059;&#x3002;&#x305F;&#x3060;&#x3057;&#x3001;&#x307B;&#x3068;&#x3093;&#x3069;&#x306E;&#x30EC;&#x30DD;&#x30FC;&#x30C8;&#x3084;&#x5473;&#x7D44;&#x7E54;&#x8FD1;&#x304F;&#x306E;&#x5C45;&#x4F4F;&#x8005;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x306E;&#x30B5;&#x30D6;&#x30BF;&#x30A4;&#x30D7; &#x3057;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x306F;&#x3001;&#x3055;&#x3089;&#x306B; T &#x7D30;&#x80DE;&#x306E; in situ &#x5065;&#x5EB7;&#x4EBA;&#x9593;&#x8338;&#x72B6;&#x4E73;&#x982D; &#xFF08;FP&#xFF09; &#x306E;&#x751F;&#x691C;&#x5185;&#x306E;&#x4E3B;&#x8981;&#x306A;&#x30B5;&#x30D6;&#x30BF;&#x30A4;&#x30D7;&#x306E;&#x4EBA;&#x53E3;&#x306E;&#x5206;&#x5E03;&#x3068;&#x7279;&#x5FB4;&#x3002;&#x514D;&#x75AB;&#x7D44;&#x7E54;&#x5316;&#x5B66;&#x7684;&#x89E3;&#x6790;&#x3092;&#x793A;&#x3057;&#x305F;&#x30D8;&#x30EB;&#x30D1;&#x30FC; T (Th) 1 (CCR5 +&#xFF09; &#x7D30;&#x80DE;&#x3092; Th2 T &#x7D30;&#x80DE;&#x3088;&#x308A;&#x3082; (CCR4 +) FP &#x3067;&#x512A;&#x52E2;&#x3060;&#x3063;&#x305F;&#x3002;Cd45ra &#x306F; + &#x30CA;&#x30A4;&#x30FC;&#x30D6; T &#x7D30;&#x80DE;&#x304C;&#x5171;&#x901A;&#x3067;&#x3042;&#x3063;&#x305F;&#x306B;&#x5BFE;&#x3057; CD45RO + &#x30E1;&#x30E2;&#x30EA;&#x30FC; T &#x7D30;&#x80DE;&#x30D7;&#x30EA;&#x30F3;&#x30B7;&#x30D1;&#x30EB;&#x306E; T &#x7D30;&#x80DE;&#x306F;&#x5473;&#x899A;&#x306E;&#x7D44;&#x7E54;&#x3067;&#x3042;&#x3063;&#x305F;&#x3002;&#x7C98;&#x819C;&#x56FA;&#x6709;&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x306E;&#x4E3B;&#x8981;&#x306A;&#x30B5;&#x30D6;&#x30BF;&#x30A4;&#x30D7; &#x30A2;&#x30EB;&#x30D5;&#x30A1;/&#x30D9;&#x30FC;&#x30BF; T &#x7D30;&#x80DE;&#x7D44;&#x7E54;&#x306E;&#x30DF;&#x30C8;&#x30B3;&#x30F3;&#x30C9;&#x30EA;&#x30A2;&#x306B;&#x95A2;&#x3059;&#x308B;&#x3001;&#x6700;&#x3082;&#x4E0A;&#x76AE;&#x9593;&#x30EA;&#x30F3;&#x30D1;&#x7403; FPs &#x306E; &gamma;&delta; T &#x7D30;&#x80DE;&#x3001;&#x3042;&#x3063;&#x305F;.&#x30EC;&#x30AE;&#x30E5;&#x30E9;&#x30C8;&#x30EA;&#x30FC; T &#x7D30;&#x80DE;&#x306E;&#x30A8;&#x30AF;&#x30B9;&#x30D7;&#x30EC;&#x30B9; CTLA 4 (CD152) &#x3068;&#x30A4;&#x30F3;&#x30BF;&#x30FC;&#x30ED;&#x30A4;&#x30AD;&#x30F3; 2 &#x53D7;&#x5BB9;&#x4F53; &#xFF08;CD25 IL-2R&#xFF09; &#x4F4E;&#x30EC;&#x30D9;&#x30EB;&#x3067; FP &#x3067;&#x767A;&#x898B;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;T &#x7D30;&#x80DE;&#x306F;&#x3001;&#x708E;&#x75C7;&#x3084;&#x611F;&#x67D3;&#x306E;&#x4FAE;&#x8FB1;&#x306B;&#x5FDC;&#x7B54;&#x3059;&#x308B;&#x6E96;&#x5099;&#x304C;&#x3067;&#x304D;&#x3066;&#x30B9;&#x30BF;&#x30F3;&#x30C9;&#x3057;&#x3001;&#x6025;&#x6027;&#x304A;&#x3088;&#x3073;&#x6162;&#x6027;&#x306E;&#x708E;&#x75C7;&#x72B6;&#x614B;&#x4E2D;&#x306B;&#x89B3;&#x6E2C;&#x5473;&#x5909;&#x5316;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3059;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x5065;&#x5EB7;&#x306A;&#x4EBA;&#x9593;&#x306E;&#x5927;&#x4EBA;&#x306E;&#x672B;&#x68A2;&#x5473;&#x7D44;&#x7E54;&#x306B;&#x304A;&#x3051;&#x308B; T &#x7D30;&#x80DE;: &#x512A;&#x52E2;&#x306A;&#x30E1;&#x30E2;&#x30EA;&#x30FC; T &#x7D30;&#x80DE;&#x3068; Th 1 &#x7D30;&#x80DE;&#x3002;

&#xAC74;&#xAC15; &#xD55C; &#xB9DB; &#xC2DC;&#xC2A4;&#xD15C;&#xC740; &#xC601;&#xC591; &#xBC0F; &#xC0B6;&#xC758; &#xC804;&#xBC18;&#xC801;&#xC778; &#xD488;&#xC9C8;, &#xC720;&#xC9C0; &#xAD00;&#xB9AC; &#xD558;&#xB294; &#xAC83;&#xC774; &#xC911;&#xC694; &#xD558; &#xACE0; &#xBBF8;&#xAC01; &#xC7A5;&#xC560;&#xB294; &#xB9CE;&#xC740; &#xC5FC;&#xC99D; &#xC131; &#xC0C1;&#xD0DC;&#xC640; &#xAD00;&#xB828;. &#xC6B0;&#xB9AC;&#xB294; &#xC774;&#xC804;&#xC5D0; &#xC815;&#xC0C1;&#xC801;&#xC778; &#xC778;&#xAC04;&#xC758; &#xBBF8;&#xAC01; &#xC870;&#xC9C1;; &#xBA74;&#xC5ED; &#xC138;&#xD3EC; &#xACB0;&#xC815; &#xADF8;&#xB4E4;&#xC740; &#xC8FC;&#xB85C; &#xC218;&#xC9C0;&#xC0C1; &#xC138;&#xD3EC;&#xC640; CD4 T &#xC138;&#xD3EC; &#xBA87; &#xB300; &#xC2DD; &#xC138;&#xD3EC;&#xC640; B &#xC138;&#xD3EC; &#xC874;&#xC7AC;&#xC785;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xC8FC;&#xBBFC; lymphocytes &#xB610;&#xB294; &#xB9DB; &#xC870;&#xC9C1; &#xADFC;&#xCC98;&#xC758; &#xD558;&#xC704;&#xC758; &#xBA87; &#xAC00;&#xC9C0; &#xBCF4;&#xACE0; &#xC788;&#xB2E4;. &#xD604;&#xC7AC;&#xC758; &#xC5F0;&#xAD6C;&#xB294; &#xCD94;&#xAC00; &#xC720;&#xD1B5; &#xBC0F; &#xAC74;&#xAC15; &#xD55C; &#xC778;&#xAC04;&#xC758; fungiform papillae (FP) biopsies &#xB0B4; &#xC6D0;&#xB798;&#xC758; &#xC7A5;&#xC18C;&#xC5D0; T &#xC138;&#xD3EC;&#xC758; &#xC8FC;&#xC694; &#xD558;&#xC704; &#xC778;&#xAD6C; &#xD2B9;&#xC9D5;. Immunohistochemical &#xBD84;&#xC11D; &#xD45C;&#xC2DC;&#xB294; T-&#xB3C4;&#xC6B0;&#xBBF8; (Th) 1 &#xC140; (CCR5 +) FP Th2 T &#xC138;&#xD3EC; (CCR4 +) &#xBCF4;&#xB2E4; &#xB354; &#xC6B0;&#xC138; &#xD588;&#xB2E4;. CD45RO + &#xBA54;&#xBAA8;&#xB9AC; T &#xC138;&#xD3EC; CD45RA + &#xC21C; &#xC9C4; T &#xC138;&#xD3EC; &#xACF5;&#xD1B5; &#xB418;&#xC9C0; &#xC54A;&#xC740; &#xBC18;&#xBA74; &#xBBF8;&#xAC01; &#xC870;&#xC9C1;&#xC5D0; &#xC8FC; T &#xC138;&#xD3EC;&#xB97C; &#xD588;&#xB2E4;. &#xC870;&#xC9C1;&#xC758; subcompartments&#xC5D0; &#xAD00;&#xD55C; Fps&#xC758; &#xAC00;&#xC7A5; intraepithelial &#xC138;&#xD3EC; lamina propria&#xC5D0;&#xC11C; &#xC138;&#xD3EC;&#xC758; &#xC8FC;&#xC694; &#xD558;&#xC704; &#xD588;&#xB2E4; &#xC54C;&#xD30C;/&#xBCA0;&#xD0C0; T &#xC138;&#xD3EC; &#xBC18;&#xBA74; &#xAC10;&#xB9C8;/&#xB378;&#xD0C0; T &#xC138;&#xD3EC;&#xB97C; &#xD588;&#xB2E4;. &#xADDC;&#xC81C; T &#xC138;&#xD3EC;&#xB294; &#xC775;&#xC2A4;&#xD504;&#xB808;&#xC2A4; CTLA-4 (CD152)&#xC640; interleukin-2 &#xC218;&#xC6A9; &#xCCB4; (IL-2 &#xB77C;&#xC6B4;&#xB4DC;, CD25) FP&#xC5D0;&#xC11C; &#xB0AE;&#xC740; &#xC218;&#xC900;&#xC5D0;&#xC11C; &#xBC1C;&#xACAC; &#xB410;&#xB2E4;. T &#xC138;&#xD3EC; &#xC5FC;&#xC99D; &#xC131; &#xBC0F; &#xC804;&#xC5FC; &#xC131; &#xBAA8;&#xC695; &#xC751;&#xB2F5;&#xD560; &#xC900;&#xBE44;&#xAC00; &#xBC0F; &#xAE09;&#xC131;&#xACFC; &#xB9CC;&#xC131; &#xC5FC;&#xC99D; &#xC0C1;&#xD0DC; &#xAD00;&#xCC30; &#xB9DB; &#xBCC0;&#xACBD;&#xC5D0; &#xC5ED;&#xD560;&#xC744; &#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC778;&#xAC04;&#xC758; &#xAC74;&#xAC15; &#xD55C; &#xC131;&#xC778;&#xC758; &#xC8FC;&#xBCC0; &#xB9DB; &#xC870;&#xC9C1;&#xC5D0; &#xC788;&#xB294; T &#xC138;&#xD3EC;: &#xC8FC;&#xB41C; &#xBA54;&#xBAA8;&#xB9AC; T &#xC138;&#xD3EC;&#xC640; Th-1 &#xC140;.

Un sistema de sabor saludable es importante para el mantenimiento de la nutrici&oacute;n y la calidad de vida, y trastornos del gusto se asocian con muchos Estados inflamatorios. Previamente determinamos las c&eacute;lulas inmunes en tejido gustativo humano normal; son c&eacute;lulas dendr&iacute;ticas predominante y las c&eacute;lulas T CD4 con algunos macr&oacute;fagos y linfocitos B presentes. Sin embargo, hay pocos informes de los subtipos de linfocitos residentes en o cerca de los tejidos de gusto. El presente estudio caracteriza la distribuci&oacute;n y la poblaci&oacute;n de los principales subtipos de c&eacute;lulas T in situ en las biopsias de papilas fungiformes humanas sanas (FP). Los an&aacute;lisis immunohistochemical indicaron que las c&eacute;lulas T-helper (Th) 1 (CCR5 +) eran m&aacute;s predominantes en FP que las c&eacute;lulas Th2 T (CCR4 +). CD45RO + c&eacute;lulas T memoria eran las principales c&eacute;lulas de T en tejido gustativo, mientras que CD45RA + c&eacute;lulas ingenuas T eran infrecuentes. Sobre subcompartimientos del tejido, m&aacute;s los linfocitos intraepiteliales de FPs eran c&eacute;lulas de gamma/delta T, mientras que el subtipo principal de linfocitos en la l&aacute;mina propia eran las c&eacute;lulas de T de Alfa/beta. C&eacute;lulas de T reguladora que expresa CTLA-4 (CD152) y receptores de interleucina-2 (IL-2R, CD25) se encontraron en niveles bajos en FP. Las c&eacute;lulas T est&aacute;n listas para responder a los insultos inflamatorias e infecciosas y pueden desempe&ntilde;ar un papel en las alteraciones del gusto observadas durante Estados inflamatorios agudos y cr&oacute;nicos.

Las c&eacute;lulas T en el tejido perif&eacute;rico gusto de adultos humanos saludables: las c&eacute;lulas de memoria predominante T y las c&eacute;lulas Th-1.

While our understanding of the molecular and cellular aspects of taste reception and signaling continues to improve, the aberrations in these processes that lead to taste dysfunction remain largely unexplored. Abnormalities in taste can develop in a variety of diseases, including infections and autoimmune disorders. In this study, we used a mouse model of autoimmune disease to investigate the underlying mechanisms of taste disorders. MRL/MpJ-Fas(lpr)/J (MRL/lpr) mice develop a systemic autoimmunity with phenotypic similarities to human systemic lupus erythematosus and Sjögren's syndrome. Our results show that the taste tissues of MRL/lpr mice exhibit characteristics of inflammation, including infiltration of T lymphocytes and elevated levels of some inflammatory cytokines. Histological studies reveal that the taste buds of MRL/lpr mice are smaller than those of wild-type congenic control (MRL/+/+) mice. 5-Bromo-2'-deoxyuridine (BrdU) pulse-chase experiments show that fewer BrdU-labeled cells enter the taste buds of MRL/lpr mice, suggesting an inhibition of taste cell renewal. Real-time RT-PCR analyses show that mRNA levels of several type II taste cell markers are lower in MRL/lpr mice. Immunohistochemical analyses confirm a significant reduction in the number of gustducin-positive taste receptor cells in the taste buds of MRL/lpr mice. Furthermore, MRL/lpr mice exhibit reduced gustatory nerve responses to the bitter compound quinine and the sweet compound saccharin and reduced behavioral responses to bitter, sweet, and umami taste substances compared with controls. In contrast, their responses to salty and sour compounds are comparable to those of control mice in both nerve recording and behavioral experiments. Together, our results suggest that type II taste receptor cells, which are essential for bitter, sweet, and umami taste reception and signaling, are selectively affected in MRL/lpr mice, a model for autoimmune disease with chronic inflammation.

Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease.

Taste buds are chemosensory structures widely distributed on the surface of the oral cavity and larynx. Taste cells, exposed to the oral environment, face great challenges in defense against potential pathogens. While immune cells, such as T-cells and macrophages, are rarely found in taste buds, high levels of expression of some immune-response-associated molecules are observed in taste buds. Yet, the cellular origins of these immune molecules such as cytokines in taste buds remain to be determined. Here, we show that a specific subset of taste cells selectively expresses high levels of the inflammatory cytokine tumor necrosis factor-α (TNF-α). Based on immuno-colocalization experiments using taste-cell-type markers, the TNF-α-producing cells are predominantly type II taste cells expressing the taste receptor T1R3. These cells can rapidly increase TNF-α production and secretion upon inflammatory challenges, both in vivo and in vitro. The lipopolysaccharide (LPS)-induced TNF-α expression in taste cells was completely eliminated in TLR2(-/-)/TLR4(-/-) double-gene-knockout mice, which confirms that the induction of TNF-α in taste buds by LPS is mediated through TLR signaling pathways. The taste-cell-produced TNF-α may contribute to local immune surveillance, as well as regulate taste sensation under normal and pathological conditions.

Expression and secretion of TNF-α in mouse taste buds: a novel function of a specific subset of type II taste cells.

The mammalian taste bud is an onion-shaped epithelial structure with 50-100 tightly packed cells, including taste receptor cells, supporting cells, and basal cells. Taste receptor cells detect nutrients and toxins in the oral cavity and transmit the sensory information to gustatory nerve endings in the buds. Supporting cells may play a role in the clearance of excess neurotransmitters after their release from taste receptor cells. Basal cells are precursor cells that differentiate into mature taste cells. Similar to other epithelial cells, taste cells turn over continuously, with an average life span of about 8-12 days. To maintain structural homeostasis in taste buds, new cells are generated to replace dying cells. Several recent studies using genetic lineage tracing methods have identified populations of progenitor/stem cells for taste buds, although contributions of these progenitor/stem cell populations to taste bud homeostasis have yet to be fully determined. Some regulatory factors of taste cell differentiation and degeneration have been identified, but our understanding of these aspects of taste bud homoeostasis remains limited. Many patients with various diseases develop taste disorders, including taste loss and taste distortion. Decline in taste function also occurs during aging. Recent studies suggest that disruption or alteration of taste bud homeostasis may contribute to taste dysfunction associated with disease and aging. 

Taste bud homeostasis in health, disease, and aging.

Although inflammatory responses are a critical component in defense against pathogens, too much inflammation is harmful. Mechanisms have evolved to regulate inflammation, including modulation by the anti-inflammatory cytokine interleukin-10 (IL-10). Previously we have shown that taste buds express various molecules involved in innate immune responses, including the proinflammatory cytokine tumor necrosis factor (TNF). Here, using a reporter mouse strain, we show that taste cells also express the anti-inflammatory cytokine IL-10. Remarkably, IL-10 is produced by only a specific subset of taste cells, which are different from the TNF-producing cells in mouse circumvallate and foliate taste buds: IL-10 expression was found exclusively in the G-protein gustducin-expressing bitter receptor cells, while TNF was found in sweet and umami receptor cells as reported previously. In contrast, IL-10R1, the ligand-binding subunit of the IL-10 receptor, is predominantly expressed by TNF-producing cells, suggesting a novel cellular hierarchy for regulating TNF production and effects in taste buds. In response to inflammatory challenges, taste cells can increase IL-10 expression both in vivo and in vitro. These findings suggest that taste buds use separate populations of taste receptor cells that coincide with sweet/umami and bitter taste reception to modulate local inflammatory responses, a phenomenon that has not been previously reported. Furthermore, IL-10 deficiency in mice leads to significant reductions in the number and size of taste buds, as well as in the number of taste receptor cells per taste bud, suggesting that IL-10 plays critical roles in maintaining structural integrity of the peripheral gustatory system. 

Interleukin-10 is produced by a specific subset of taste receptor cells and critical for maintaining structural integrity of mouse taste buds.

Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. 

Regulation of bitter taste responses by tumor necrosis factor.

Inflammatory bowel disease (IBD) is a debilitating immune-related condition that affects over 1.4 million Americans. Recent studies indicate that taste receptor signaling is involved in much more than sensing food flavor, and taste receptors have been localized in a variety of extra-oral tissues. One of the newly revealed functions of taste receptors and downstream signaling proteins is modulation of immune responses to microbes and parasites. We previously found that components of the taste receptor signaling pathway are expressed in subsets of the intestinal epithelial cells. α-Gustducin, a key G-protein α subunit involved in sweet, umami, and bitter taste receptor signaling, is expressed in the intestinal mucosa. In this study, we investigated the role of α-gustducin in regulation of gut mucosal immunity and inflammation using α-gustducin knockout mice in the dextran sulfate sodium (DSS)-induced IBD model. DSS is a chemical colitogen that can cause intestinal epithelial damage and inflammation. We analyzed DSS-induced colitis in α-gustducin knockout versus wild-type control mice after administration of DSS in drinking water. Our results show that the knockout mice had aggravated weight loss, diarrhea, intestinal bleeding, and inflammation over the experimental period compared to wild-type mice, concurrent with augmented immune cell infiltration and increased expression of TNF and IFN-γ but decreased expression of IL-13 and IL-5 in the colon. These results suggest that the taste receptor signaling pathway may play critical roles in regulating gut immune balance and inflammation.

Pu Feng

Monell Chemical Senses Center

Effects of Taste Signaling Protein Abolishment on Gut Inflammation in an Inflammatory Bowel Disease Mouse Model