Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, P R China.
Eur J Immunol. 2010 Apr;40(4):1079-88. doi: 10.1002/eji.200940015.
Complement 5a (C5a) and Interleukin-17 (IL-17) are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL-17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate of mice following cecal ligation and puncture (CLP)-induced sepsis and decreased IL-17 expression in vivo. IL-17 was secreted mainly by gammadelta T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL-17 secretion by gammadelta T cells. Dendritic cells (DC) were found to act as a "bridge" between C5a and gammadelta T cells in a mechanism involving IL-6 and transforming growth factor beta (TGF-beta). These results imply that C5a affects the crosstalk between DC and gammadelta T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL-17.
补体 5a（C5a）和白细胞介素-17（IL-17）是脓毒症中两种重要的炎症介质。在这里，我们研究了过敏毒素 C5a 调节 IL-17 的机制。我们发现，C5a 阻断可提高盲肠结扎和穿刺（CLP）诱导的脓毒症小鼠的存活率，并降低体内的 IL-17 表达。在该模型中，IL-17 主要由 gammadelta T 细胞分泌。重要的是，我们的数据表明 C5a 参与了 gammadelta T 细胞分泌 IL-17 的调节。发现在涉及白细胞介素 6（IL-6）和转化生长因子β（TGF-β）的机制中，树突状细胞（DC）充当 C5a 和 gammadelta T 细胞之间的“桥梁”。这些结果表明，C5a 影响脓毒症发展过程中 DC 和 gammadelta T 细胞之间的串扰，这可能导致大量炎症介质如 IL-17 的产生。
