Complement C5a regulates IL-17 by affecting the crosstalk between DC and γδ T cells in CLP-induced sepsis

Abstract

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 γδ T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL-17 secretion by γδ T cells. Dendritic cells (DC) were found to act as a "bridge" between C5a and γδ T cells in a mechanism involving IL-6 and transforming growth factor β (TGF-β). These results imply that C5a affects the crosstalk between DC and γδ T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL-17. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.