IFN-γ Limits Th9-Mediated Autoimmune Inflammation through Dendritic Cell Modulation of IL-27

被引：67

作者：

Murugaiyan, Gopal

Beynon, Vanessa

Da Cunha, Andre Pires

Joller, Nicole

Weiner, Howard L. ^{[1
,2
]}

机构：

[1] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

JOURNAL OF IMMUNOLOGY | 2012年 / 189卷 / 11期

基金：

美国国家卫生研究院;

关键词：

CD4(+) T-CELLS; CENTRAL-NERVOUS-SYSTEM; ALLERGIC INFLAMMATION; CUTTING EDGE; ENCEPHALOMYELITIS; DIFFERENTIATION; INTERLEUKIN-27; INDUCTION; MICE; PROLIFERATION;

D O I：

10.4049/jimmunol.1200808

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

IL-9-producing Th9 cells have been associated with autoimmune diseases, such as experimental autoimmune encephalitis. However, the factors that negatively regulate Th9 cells during autoimmune inflammation are unclear. In this article, we show that IFN-gamma inhibits Th9 differentiation both in vitro and in vivo. This suppressive activity was dependent on the transcription factor STAT-1. In addition to its direct inhibitory effect on Th9 differentiation, IFN-gamma suppressed Th9 cells through the induction of IL-27 from dendritic cells. In vitro, treatment of naive CD4(+) T cells with IL-27 suppressed the development of Th9 cells, which was partially dependent on the transcription factors STAT-1 and T-bet. Moreover, IL-27 treatment completely abrogated the encephalitogenicity of Th9 cells in the experimental autoimmune encephalomyelitis model. Thus, our results identify a previously unknown mechanism by which IFN-gamma limits Th9-mediated autoimmune inflammation through dendritic cell modulation of IL-27. The Journal of Immunology, 2012, 189: 5277-5283.

引用

页码：5277 / 5283

页数：7

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