IRF-4-Binding Protein Inhibits Interleukin-17 and Interleukin-21 Production by Controlling the Activity of IRF-4 Transcription Factor

被引：164

作者：

Chen, Qinzhong ^{[1
]}

Yang, Wen ^{[1
]}

Gupta, Sanjay ^{[1
]}

Biswas, Partha ^{[1
]}

Smith, Paula ^{[2
]}

Bhagat, Govind ^{[2
]}

Pernis, Alessandra B. ^{[1
]}

机构：

[1] Columbia Univ, Dept Med, New York, NY 10032 USA

[2] Columbia Univ, Dept Pathol, New York, NY 10032 USA

来源：

IMMUNITY | 2008年 / 29卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.immuni.2008.10.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The T helper 17(Th17) cell lineage is important in inflammatory and autoimmune responses, via its ability to produce interleukin-17 (IL-17) and IL-21. Given the potentially deleterious effects of Th17 cells, their generation needs to be strictly controlled. IRF-4 is a transcription factor that has recently emerged as a key regulator of Th17 cell differentiation. Here, we showed that mice deficient in a previously isolated protein, IBP (IRF-4-binding protein), rapidly developed rheumatoid arthritis-like joint disease and large-vessel vasculitis. The pathology was associated with an enhanced responsiveness of T cells to low levels of stimulation and with the inappropriate synthesis of IL-17 and IL-21. IBP sequestered IRF-4 and prevented it from targeting the transcriptional regulatory regions of the genes that encode IL-17 and IL-21. Thus, IBP appears to be important in preventing T cell-mediated autoimmunity by ensuring that the production of IL-17 and IL-21 does not occur in response to self-antigens.

引用

页码：899 / 911

页数：13

共 55 条

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