Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORγt

被引:86
|
作者
Yang, Jianfei [1 ]
Yang, Min [2 ]
Htut, Tin Min [1 ]
Ouyang, Xinshou [2 ]
Hanidu, Adedayo [1 ]
Li, Xiang [1 ]
Sellati, Rosemarie [1 ]
Jiang, Huiping [3 ]
Zhang, Shu [4 ]
Li, Hongxing [2 ]
Zhao, Jie [2 ]
Ting, Adrian T. [2 ]
Mayer, Lloyd [2 ]
Unkeless, Jay C. [2 ]
Labadia, Mark E. [1 ]
Hodge, Martin [1 ]
Li, Jun [1 ]
Xiong, Huabao [2 ]
机构
[1] Boehringer Ingelheim Pharmaceut Inc, Dept Immunol & Inflammat, Ridgefield, CT 06877 USA
[2] Mt Sinai Sch Med, Immunobiol Ctr, New York, NY USA
[3] Boehringer Ingelheim Pharmaceut Inc, Dept Translat Sci, Ridgefield, CT 06877 USA
[4] Mt Sinai Sch Med, Dept Pediat, New York, NY USA
关键词
cytokines; gene regulation; T helper cells;
D O I
10.1002/eji.200838145
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 to form IL-27 and with IL-12p35 to form IL-35. IL-27R alpha(-/-) mice studies indicate that IL-27 negatively regulates Th17 cell differentiation. However, no EBI3, p28 or p35-deficiency studies that directly address the role of EBI3, p28 or p35 on Th17 cells have been done. Here, we demonstrate that spleen cells derived from EBI3(-/-) mice produce significantly higher levels of IL-17 as well as IL-22 upon stimulation with OVA. in vitro derived EBI3(-/-) Th.17 cells also produced significantly higher levels of IL-17 and IL-22 than WT cells. The frequency of IL-17-producing cells was also elevated when EBI3(-/-) cells were cultured under Th17 conditions. In addition, spleen cells from EBI3(-/-) mice immunized with Listeria monocytogenes produced significantly elevated levels of IL-17 and IL-22. Furthermore, the Th17 transcription factor ROR gamma t was significantly enhanced in EBI3(-/-) cells. Finally, EBI3(-/-) mice exhibited a reduced bacterial load following an acute challenge with L. monocytogenes or a re-challenge of previously immunized mice, suggesting that EBI3 negatively regulates both innate and adaptive immunity. Taken together, these data provide direct evidence that EBI3 negatively regulates the expression of IL-17, IL-22 and ROR gamma t as well as protective immunity against L. monocytogenes.
引用
收藏
页码:1204 / 1214
页数:11
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