Modulatory effects of decoy receptor 3 on T cell and macrophage differentiation and activation

• Main Authors: Yung-Chi Chang, 張永祺
• Other Authors: Shie-Liang Hsieh
• Format: Others
• Language: en_US
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/13607995808996348246

碩士 === 國立陽明大學 === 微生物暨免疫學研究所 === 89 === Activation of members of TNFR superfamily are involved in the regulation of pleiotropic biological processes such as cell proliferation, differentiation, apoptosis, cytokine production. Recently, a novel member of the TNFR superfamily, DcR3, was identified as soluble cognate receptor for LIGHT and Fas ligand (FasL). In our previous study [60], we found that DcR3 could be detected in the serum, and bind to the surface of monocytes, B cells, but not T cells. Therefore, we are interested to understand whether it has any modulatory effects on host immune system, in addition to its neutralizing effect of FasL and LIGHT. To address this question, human CD4+ T cells and CD14+ monocyte-derived macrophages were used to test our hypothesis. We found that DcR3 did not have obvious effects to regulate T cell proliferation of normal individuals, however, DcR3 had profound effects on macrophage differentiation and activation. The expression of CD86 on macrophages was up-regulated, while CD14, CD16, CD80 and HLA-DR were down-regulated by DcR3. Moreover, phagocytic activity of macrophages was almost completely inhibited by DcR3, and DcR3-treated macrophages were also impaired to secrete IL-1b, IL-6, TNF-a and synthesize iNOS in response to LPS stimulation. In contrast to the inflammatory reactions, the secretion of immune-suppressive cytokine, such as TGF-b1, was not completely suppressed by DcR3, although DcR3 inhibited the engulfment of apoptotic cells by macrophages. The diverse regulatory effects of DcR3 were not via neutralizing FasL and LIGHT, and this observation raised the argument that the DcR3 should not be simply regarded as soluble receptor, but as an effective molecule to modulate host immunity and protect tumor cells from attack of host immune system.