Th17 cytokines and their emerging roles in inflammation and autoimmunity

被引:186
作者
Fouser, Lynette A. [1 ]
Wright, Jill F. [1 ]
Dunussi-Joannopoulos, Kyriaki [1 ]
Collins, Mary [1 ]
机构
[1] Wyeth Res Inflammat, Cambridge, MA 02140 USA
关键词
Th1/Th2/Th17; cells; cytokines; cytokine receptors; inflammation; autoimmunity;
D O I
10.1111/j.1600-065X.2008.00712.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T-helper 17 (Th17) cells are a new lineage of CD4(+) T cells that are characterized by their production of interleukin-17A (IL-17A). Recent studies show that these cells can also express IL-17F, IL-22, and IL-21. IL-17A and IL-17F can form a heterodimeric cytokine, which mediates biological activities, at least in part, through shared receptors with IL-17A and IL-17F homodimers. The cytokines made by Th17 cells represent three distinct gene families, highlighting the unique biology of these cells. Accumulating data support a role for Th17 cells and these cytokines in inflammatory processes and in animal models of autoimmunity or inflammation. Emerging data in clinical trials support our understanding of the importance of Th17 cells in inflammatory disease. Future clinical studies will allow us to evaluate the role of each cytokine independently in contributing to human diseases with immune-mediated pathologies and to design optimal cytokine-targeted therapies for these diseases.
引用
收藏
页码:87 / 102
页数:16
相关论文
共 148 条
[1]   Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].
Aggarwal, S ;
Ghilardi, N ;
Xie, MH ;
de Sauvage, FJ ;
Gurney, AL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914
[2]   Interleukin 6 is required for the development of collagen-induced arthritis [J].
Alonzi, T ;
Fattori, E ;
Lazzaro, D ;
Costa, P ;
Probert, L ;
Kollias, G ;
De Benedetti, F ;
Poli, V ;
Ciliberto, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (04) :461-468
[3]   Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts [J].
Andoh, A ;
Zhang, ZB ;
Inatomi, O ;
Fujino, S ;
Deguchi, Y ;
Araki, Y ;
Tsujikawa, T ;
Kitoh, K ;
Kim-Mitsuyama, S ;
Takayanagi, A ;
Shimizu, N ;
Fujiyama, Y .
GASTROENTEROLOGY, 2005, 129 (03) :969-984
[4]   Serum levels of TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17 and IL-18 in patients with active psoriasis and correlation with disease severity [J].
Arican, O ;
Aral, M ;
Sasmaz, S ;
Ciragil, P .
MEDIATORS OF INFLAMMATION, 2005, (05) :273-279
[5]   IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia [J].
Aujla, Shean J. ;
Chan, Yvonne R. ;
Zheng, Mingquan ;
Fei, Mingjian ;
Askew, David J. ;
Pociask, Derek A. ;
Reinhart, Todd A. ;
McAllister, Florencia ;
Edeal, Jennifer ;
Gaus, Kristi ;
Husain, Shahid ;
Kreindler, James L. ;
Dubin, Patricia J. ;
Pilewski, Joseph M. ;
Myerburg, Mike M. ;
Mason, Carol A. ;
Iwakura, Yoichiro ;
Kolls, Jay K. .
NATURE MEDICINE, 2008, 14 (03) :275-281
[6]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[7]   Induction and effector functions of TH17 cells [J].
Bettelli, Estelle ;
Korn, Thomas ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE, 2008, 453 (7198) :1051-1057
[8]   Th17: the third member of the effector T cell trilogy [J].
Bettelli, Estelle ;
Korn, Thomas ;
Kuchroo, Vijay K. .
CURRENT OPINION IN IMMUNOLOGY, 2007, 19 (06) :652-657
[9]   Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism [J].
Bleicher, Lucas ;
de Moura, Patricia Ribeiro ;
Watanabe, Leandra ;
Colau, Didier ;
Dumoutier, Laure ;
Renauld, Jean-Christophe ;
Polikarpov, Igor .
FEBS LETTERS, 2008, 582 (20) :2985-2992
[10]   IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes [J].
Boniface, K ;
Bernard, FX ;
Garcia, M ;
Gurney, AL ;
Lecron, JC ;
Morel, F .
JOURNAL OF IMMUNOLOGY, 2005, 174 (06) :3695-3702