Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice

被引：589

作者：

Hsu, Hui-Chen ^{[1
]}

Yang, PingAr ^{[1
]}

Wang, John ^{[1
]}

Wu, Qi ^{[1
]}

Myers, Riley ^{[1
]}

Chen, Jian ^{[1
]}

Yi, John ^{[2
]}

Guentert, Tanja ^{[1
]}

Tousson, Albert ^{[3
]}

Stanus, Andrea L. ^{[4
]}

Le, Thuc-vy L. ^{[2
]}

Lorenz, Robin G. ^{[4
]}

Xu, Hui ^{[5
]}

Kolls, Jay K. ^{[6
]}

Carter, Robert H. ^{[1
,7
]}

Chaplin, David D. ^{[2
]}

Williams, Robert W. ^{[8
]}

Mountz, John D. ^{[1
,7
]}

机构：

[1] Univ Alabama, Dept Med, Birmingham, AL 35294 USA

[2] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA

[3] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA

[4] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA

[5] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA

[6] Childrens Hosp Pittsburgh, Dept Pediat Pulmonol, Pittsburgh, PA 15213 USA

[7] Vet Adm Med Ctr, Birmingham, AL 35233 USA

[8] Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN 38152 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 02期

关键词：

SPONTANEOUS EROSIVE ARTHRITIS; GTPASE-ACTIVATING PROTEINS; INDUCED CYTIDINE DEAMINASE; COLLAGEN-INDUCED ARTHRITIS; INBRED MOUSE STRAINS; B-CELLS; PATHOGENIC AUTOANTIBODIES; AFFINITY MATURATION; FAMILY-MEMBERS; ALPHA-SUBUNITS;

D O I：

10.1038/ni1552

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interleukin 17 (IL-17) is a cytokine associated with inflammation, autoimmunity and defense against some bacteria. Here we show that IL-17 can promote autoimmune disease through a mechanism distinct from its proinflammatory effects. As compared with wild-type mice, autoimmune BXD2 mice express more IL-17 and show spontaneous development of germinal centers (GCs) before they increase production of pathogenic autoantibodies. We show that blocking IL-17 signaling disrupts CD4(+) T cell and B cell interactions required for the formation of GCs and that mice lacking the IL-17 receptor have reduced GC B cell development and humoral responses. Production of IL-17 correlates with upregulated expression of the genes Rgs13 and Rgs16, which encode regulators of G-protein signaling, and results in suppression of the B cell chemotactic response to the chemokine CXCL12. These findings suggest a mechanism by which IL-17 drives autoimmune responses by promoting the formation of spontaneous GCs.

引用

页码：166 / 175

页数：10

共 47 条

[1] Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5 [J].