C5a regulates IL-12+ DC migration to induce pathogenic Th1 and Th17 cells in sepsis.
OBJECTIVE
It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs) to stimulate adaptive immune cells such as Th1 and Th17 in sepsis.


METHODS
Sepsis was induced by cecal ligation and puncture (CLP). CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+)DC, IFNγ(+)Th1, and IL-17(+)Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA.


RESULTS
Our studies here showed that C5a induced IL-12(+)DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+)DC cells induced the expansion of pathogenic IFNγ(+)Th1 and IL-17(+)Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis.


CONCLUSIONS
Our data suggests that C5a regulates IL-12(+)DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
Ning
N
Ma
Chen
C
Xing
He
H
Xiao
Yi
Y
Wang
Ke
K
Wang
Chunmei
C
Hou
Gencheng
G
Han
Guojiang
G
Chen
Bernadette
B
Marrero
Yujuan
Y
Wang
Beifen
B
Shen
Yan
Y
Li
Renxi
R
Wang
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002432:Cecum / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D015936:Complement C5a / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D018664:Interleukin-12 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D008026:Ligation; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; D011677:Punctures; D018805:Sepsis / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000473:pathology*; D058504:Th17 Cells / Q000187:drug effects / Q000473:pathology*
D039521:CD11c Antigen; D020011:Protective Agents; D018664:Interleukin-12; D015936:Complement C5a