Induction and molecular signature of pathogenic TH17 cells

被引：890
|
作者：
Lee, Youjin [1 ]
Awasthi, Amit [1 ]
Yosef, Nir [1 ,2 ]
Quintana, Francisco J. [1 ]
Xiao, Sheng [1 ]
Peters, Anneli [1 ]
Wu, Chuan [1 ]
Kleinewietfeld, Markus [3 ]
Kunder, Sharon [1 ]
Hafler, David A. [3 ]
Sobel, Raymond A. [4 ,5 ]
Regev, Aviv [2 ,6 ]
Kuchroo, Vijay K. [1 ]
机构：
[1] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med, Boston, MA 02115 USA
[2] Broad Inst MIT & Harvard, Cambridge, MA USA
[3] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
[4] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
[5] Stanford Univ, Palo Alto Vet Adm Hlth Care Syst, Sch Med, Stanford, CA 94305 USA
[6] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA USA
来源：
NATURE IMMUNOLOGY | 2012年 / 13卷 / 10期
基金：
美国国家卫生研究院;
关键词：
T-CELLS; IFN-GAMMA; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; AUTOIMMUNE ENCEPHALOMYELITIS; INTERLEUKIN-7; RECEPTOR; TRANSCRIPTION FACTOR; DIFFERENTIATION; CYTOKINE; TH1;
D O I：
10.1038/ni.2416
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)-producing helper T cells (T(H)17 cells) are often present at the sites of tissue inflammation in autoimmune diseases, which has led to the conclusion that T(H)17 cells are main drivers of autoimmune tissue injury. However, not all T(H)17 cells are pathogenic; in fact, T(H)17 cells generated with transforming growth factor-beta 1 (TGF-beta 1) and IL-6 produce IL-17 but do not readily induce autoimmune disease without further exposure to IL-23. Here we found that the production of TGF-beta 3 by developing T(H)17 cells was dependent on IL-23, which together with IL-6 induced very pathogenic T(H)17 cells. Moreover, TGF-beta 3-induced T(H)17 cells were functionally and molecularly distinct from TGF-beta 1-induced T(H)17 cells and had a molecular signature that defined pathogenic effector T(H)17 cells in autoimmune disease.
引用
收藏
页码：991 / 999
页数：9
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