| Summary: | 碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系暨研究所 === 98 === Experimental autoimmune encephalomyelitis (EAE) is a useful animal model for human multiple sclerosis (MS) which is an autoimmune demyelinating disease mediated by CD4+ T cell affecting the central nervous system(CNS). Previous studies have indicated that IFN-??producing Th1 cells and IL-17-producing Th17 cells play important roles in the pathogenesis of EAE. In addition, regulatory T cells (Tregs) also have been demonstrated as a negative regulator of immune responses in clinical diseases such as rheumatoid arthritis and systemic lupus erythematosus.
TREMs (Triggering receptor expressed on myeloid cells), a family of membrane receptors using DAP12 as signaling molecule, belong to the immunoglobulin superfamily and are expressed in many immune cells such as neutrophils, dendritic cells and macrophages etc. Many studies have shown that TREM2 and DAP12 possess inflammatory response and pathogenesis of experimental autoimmune encephalomyelitis. For example, blockade of TREM-2 by monoclonal antibody exacerbates experimental autoimmune encephalomyelitis and DAP12-/- mice fail to develop pathogenesis of experimental autoimmune encephalomyelitis. Additionally, TREM-1 serves as an inflammation amplifier in immune system. However, the function of TREM-3 still remains unclear.
In this study, we investigate the immuno-modulatory effects of TREM-3 in EAE mice through the comparison of EAE induction with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in C57BL/6 and TREM3-/- mice. MOG-induced proliferation and Th1- and Th17-secreting cytokines such as IL-2, IFN-? and IL-17 were suppressed in TREM3-/- mice. We also found that the spinal cords of TREM3-/- mice had less infiltration of inflammatory mononuclear cells. Moreover, expression of TREM3 gene is higher in EAE mice compared with that of wild-type mice. These results suggest that TREM3 receptors play some important roles in the development of experimental autoimmune encephalomyelitis.
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