车站3
先天性淋巴细胞
柠檬酸杆菌
生物
RAR相关孤儿受体γ
转录因子
免疫学
白细胞介素6
白细胞介素22
白细胞介素17
癌症研究
先天免疫系统
细胞因子
白细胞介素
细胞生物学
信号转导
病菌
免疫系统
基因
遗传学
作者
Xiaohuan Guo,Ju Qiu,Tony Tu,Xuanming Yang,Liufu Deng,Robert A. Anders,Liang Zhou,Yang Xin Fu
出处
期刊:Immunity
[Elsevier]
日期:2014-01-16
卷期号:40 (1): 25-39
被引量:186
标识
DOI:10.1016/j.immuni.2013.10.021
摘要
Inhibitors of the transcription factor STAT3 target STAT3-dependent tumorigenesis but patients often develop diarrhea from unknown mechanisms. Here we showed that STAT3 deficiency increased morbidity and mortality after Citrobacter rodentium infection with decreased secretion of cytokines including IL-17 and IL-22 associated with the transcription factor RORγt. Administration of the cytokine IL-22 was sufficient to rescue STAT3-deficient mice from lethal infection. Although STAT3 was required for IL-22 production in both innate and adaptive arms, by using conditional gene-deficient mice, we observed that STAT3 expression in RORγt(+) innate lymphoid cells (ILC3s), but not T cells, was essential for the protection. However, STAT3 was required for RORγt expression in T helper cells, but not in ILC3s. Activated STAT3 could directly bind to the Il22 locus. Thus, cancer therapies that utilize STAT3 inhibitors increase the risk for pathogen-mediated diarrhea through direct suppression of IL-22 from gut ILCs.
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