Complement C5a regulates IL-17 by affecting the crosstalk between DC and gammadelta T cells in CLP-induced sepsis.
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.
Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, P R China.
Ruonan
R
Xu
Renxi
R
Wang
Gencheng
G
Han
Jianan
J
Wang
Guojiang
G
Chen
Liyan
L
Wang
Xia
X
Li
Renfeng
R
Guo
Beifen
B
Shen
Yan
Y
Li
D019264:Adoptive Transfer; D000818:Animals; D002432:Cecum / Q000293:injuries; D002450:Cell Communication / Q000502:physiology*; D018920:Coculture Techniques; D015936:Complement C5a / Q000494:pharmacology / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D007416:Intestinal Perforation / Q000150:complications; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000209:etiology / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
C098680:Il17a protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins; D015936:Complement C5a