Study on the modulatroy effect of prostaglandin I2 on regulatory T cell differentiation

• Main Authors: Yu-Fang Chen, 陳俞方
• Other Authors: Jau-Ling Suen
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/17720735590800290942

碩士 === 高雄醫學大學 === 醫學研究所 === 100 === Background：It has been shown that prostaglandin I2 (PGI2)-IP signaling has an anti-inflammatory effect and displays an ability to modulate immune responses. It has been shown that PGI2-IP signaling can modulate dendritic cell (DC) into tolerogenic phenotype. However, whether PGI2-IP signaling modulates regulatory T-cell differentiation and function via DCs is still unclear. Methods：Murine bone marrow-derive DCs (BM-DCs) treated with PGI2 analog (iloprost) following LPS stimulation were analyzed their phenotype, tolerogenic associated molecules and function. Using co-culture and adoptive transfer experiments to examine whether iloprost-modulating DCs affect naïve CD4+ T cells differentiate into Treg cells in vitro and in vivo. Neutralizing monoclonal antibodies were used to clarify which molecule involves in the adaptive Treg differentiation mediated by iloprost-treated DCs. Results：Our data showed that iloprost modulated DCs displayed immature phenotype with low expression of CD40, CD80, CD86 and MHC class II. Iloprost modulated DCs promoted antigen-specific adaptive Treg cells differentiation in vitro and in vivo. In addition, iloprost also enhanced the expression of tolerogenic associated molecules in DCs, including PD-L1, ICOS-L, CD73, CD39 and IDO. We found that iloprost modulated DCs promoted Treg cells differentiation, at least in part , through PD-L1 expression. Conclusions：Our study demonstrated that iloprost modulated DCs promote antigen-specific Foxp3+ Treg cell differentiation through enhanced PD-L1 expression. This study helps us to understand the mechanism of tolerance induction by PGI2-IP signaling, and to explore strategies to design immunotherapy for inflammatory diseases.