induction-diverse-assessment-indicators-experimental-autoimmune

Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a typical autoimmune disease of the central nervous system (CNS) characterized by inflammatory infiltration, demyelination, and ...

Tongji University

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelinating neuropathy. The etiology of MS is not yet clear and its treatment remains a major medical challenge. While we search for drugs that can effectively treat experimental autoimmune encephalomyelitis (EAE), the animal model of MS, we also hope to further explore its possible pathogenesis. In the present study, we investigated whether methyl butyrate (MB) could alleviate EAE and its potential mechanisms. In EAE mice, we found that administration of MB was effective in alleviating their clinical signs and improving histopathological manifestations of the CNS. In the CNS and intestinal lamina propria, we observed fewer effector T cells, including Th1 and Th17, in the MB-treated group. MB also increased the proportion of regulatory T cells and the secretion of IL-10 in peripheral immune organs. In vitro, MB led to suppression of Th1 cells and promotion of regulatory T cells in their differentiation. Given that MB had no direct effect on Th17 cell differentiation in vitro, we hypothesized that MB suppressed Th17 cells indirectly by inhibiting the secretion of IL-6, which was later confirmed both in vitro and in vivo. In addition, we found that MB treatment upregulated Maf gene expression in mice, which explained its promotion of IL-10 secretion. The above findings suggest that MB may provide new ideas for the study of the mechanism of MS and have positive implications for new drug development.

Methyl Butyrate Alleviates Experimental Autoimmune Encephalomyelitis and Regulates the Balance of Effector T Cells and Regulatory T Cells.

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) mediated by immune cells. The pathogenesis of most autoimmune diseases has some degree of similarity to that of MS, and therefore the study of MS has clinical and scientific significance for other autoimmune diseases as well. As a widely used organic solvent, Methyl Acetate (MA) has a similar structure to acetate which has been shown to be therapeutic in the mouse model of multiple sclerosis. Here we found that MA was effective in reducing the disease severity of Experimental Autoimmune Encephalomyelitis (EAE). Pathological sections showed that MA reduced inflammatory cell infiltration in the CNS and attenuated demyelination in the spinal cord. MA increases the proportion of Th1 cells in the periphery of EAE mice. Further mechanistic studies have demonstrated that MA treatment induces Th1 retention in the peripheral immune system by increasing the expression levels of peripheral Th1-related chemokines CXCR3. CXCL9, CXCL10. In addition, we observed that MA alleviated intestinal inflammation in EAE mice. The data showed that this phenomenon is achieved by enhancing IL-10 and inhibiting IL-6 secretion. Our data indicates that MA might have therapeutic implications for autoimmune diseases such as MS.

Methyl acetate arrests Th1 in peripheral immune system and alleviates CNS inflammation in EAE.

Multiple sclerosis (MS) was one of the major conditions causing neurological dysfunction and was an incurable progressive central nervous system disease. Experimental autoimmune encephalomyelitis (EAE) was the most commonly used experimental model of MS. Artemisinin have been shown to exhibit anti-inflammatory effects through unclear mechanisms. In this study, we aimed to evaluate the effect of administration of the artemisinin derivative TPN10466 in EAE. TPN10466 alleviated the severity of disease in EAE. Further studies showed that TPN10466 inhibited lymphocyte migration by downregulating chemokine expression and adhesion molecules. In addition, studies showed that TPN10466 directly inhibited Th1 and Th17 differentiation and reduced Th1 and Th17 infiltration into the central nervous system. In conclusion, our work demonstrated that TPN10466 provided protection against the autoimmune disease EAE by inhibiting the migration of immune cells and suppressing Th1/Th17 differentiation, suggesting that TPN10466 could be a potential for promising potential agent for the treatment of MS/EAE.

Artemisinin derivative TPN10466 suppresses immune cell migration and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis.

Kaidireya Saimaier

Putuo People's Hospital,
Shanghai Key Laboratory of Signaling and Disease Research,
School of Life Sciences and Technology,
Putuo People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology

Tongji University

Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis