Cutting edge: CTLA-4--B7 interaction suppresses Th17 cell differentiation.
Th cells that produce IL-17 (Th17 cells) are a distinct subset of Th cells implicated in several autoimmune diseases. Although CD28-B7 interaction has been shown to be involved in Th17 differentiation in vitro, the role of CTLA-4 in controlling Th17 development is completely unknown. We report in this paper that blocking the CTLA-4-B7 interaction potentiates Th17 cell differentiation in vitro and in vivo. Furthermore, blocking CTLA-4-B7 interaction in vivo confers the susceptibility of experimental autoimmune myocarditis to CD28(-/-) mice or increases the severity of experimental autoimmune myocarditis in wild-type mice. The enhanced disease susceptibility is mediated by heightened Th17 responses. With these results, we are the first to demonstrate that CTLA-4-B7 interaction inhibits Th17 differentiation in vitro and in vivo and suppresses Th17-mediated autoimmunity.
Ying
Haiyan
H
Laboratory of Molecular Cancer Biology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Yang
Lifen
L
Qiao
Guilin
G
Li
Zhenping
Z
Zhang
Li
L
Yin
Fei
F
Xie
Dong
D
Zhang
Jian
J
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018106:CD28 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D006131:Growth Inhibitors; D020381:Interleukin-17