Immunomodulatory effect of decoy receptor 3 on bone marrow-derived dendritic cells from non-obese diabetic mice

• Main Authors: Tan-Mei Liu, 劉譚美
• Other Authors: Huey-Kang Sytwu
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/40387591323602363713

碩士 === 國防醫學院 === 微生物及免疫學研究所 === 91 === Insulin-dependent diabetes mellitus (IDDM), also named type I, or juvenile-onset diabetes, is a kind of autoimmune disease. The non-obese diabetic (NOD) mouse, an inbred strain that spontaneously develops autoimmune diabetes resembling human IDDM is a widely used animal model for dissecting immunopathological mechanisms in IDDM and developing preventive and/or therapeutic strategies. Decoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and is first found to be overexpressed by malignant tumors arising from pulmonary and gastrointestinal tract. DcR3 can bind with FasL and inhibit T-lymphocytes induced apoptosis that may be one of the possible mechanisms for tumor cells to escape the immunosurveillance. It has recently been reported that DcR3-treated dendritic cells (DCs) that differentiated from human peripheral monocytes, expressed higher level of CD86 and biased T cell differentiation to the T helper 2 (Th2) phenotype. Therefore, in this study, we tested whether DcR3 can modulate the differentiation and maturation of bone marrow-derived DCs (BM-DCs) from NOD mice, and induced T cell differentiation to the Th2 phenotype. Our study revealed that CD86 was up-regulated, and CD11c, CD80, CD40, and MHC I-Ag7 were down-regulated, and CD54 were not affected on DcR3.Fc-treated DCs. The proliferation of CD4+ T cells co-cultured with DcR3.Fc-treated DCs was significantly decreased, when compared to that of T cells stimulated by regular DCs. Furthermore, we found DcR3.Fc-treated DCs had higher ERK MAP kinase activity and MAP kinase-mediated signal transduction is involved in DC maturation and function. The use of MAP kinase inhibitors also help us to understand that the distribution of surface markers of DCs related to cytokine secretion and the expression of MAP kinase.