NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis.
NFIL3-deficient mice develop microbiota-dependent, IL-12/23-driven spontaneous colitis.
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DOI：
10.4049/jimmunol.1301819
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发表时间：
2014-02-15
期刊：
影响因子：
--
通讯作者：
Plevy SE
中科院分区：
文献类型：
--
作者：
Kobayashi T;Steinbach EC;Russo SM;Matsuoka K;Nochi T;Maharshak N;Borst LB;Hostager B;Garcia-Martinez JV;Rothman PB;Kashiwada M;Sheikh SZ;Murray PJ;Plevy SE
NFIL3(核因子，IL-3调节因子)是一种调节多种免疫功能的转录因子。在髓系细胞中，NFIL3是IL-10诱导的，并作为IL-12p40转录抑制因子发挥关键作用。NFIL3是人类炎症性肠病的易感基因。在这里，我们描述了Nfil3−/−小鼠的自发性结肠炎。同时缺乏NFIL3和IL10(NIDKO)的小鼠有严重的早发性结肠炎，这表明NFIL3和IL-10独立地调节粘膜的动态平衡。淋巴细胞对于结肠炎是必需的，因为Nfil3/Rag1双基因敲除(NRDKO)小鼠对疾病具有保护作用。然而，与Rag1−/−受体相比，过继转移野生型cd4+T细胞的NRDKO小鼠患上了严重的结肠炎，这表明结肠炎与先天免疫细胞缺陷有关。在Nfil3/Il12b双缺陷小鼠中，结肠炎被消除，确定Il12b调节失调是一种中心致病事件。最后，无菌的Nfil3−/−小鼠没有结肠炎。因此，NFIL3是一种微生物区系依赖、IL-10非依赖的黏膜动态平衡调节因子，通过IL-12p40调节。
NFIL3 (nuclear factor, IL-3 regulated) is a transcription factor that regulates multiple immunologic functions. In myeloid cells, NFIL3 is IL-10 inducible, and has a key role as a repressor of IL-12p40 transcription. NFIL3 is a susceptibility gene for the human inflammatory bowel diseases. Here we describe spontaneous colitis in Nfil3−/− mice. Mice lacking both Nfil3 and Il10 (NIDKO) had severe early-onset colitis, suggesting NFIL3 and IL-10 independently regulate mucosal homeostasis. Lymphocytes were necessary for colitis, as Nfil3/Rag1 double knockout (NRDKO) mice were protected from disease. However, NRDKO mice adoptively transferred with wild type CD4+ T cells developed severe colitis compared to Rag1−/− recipients, suggesting that colitis was linked to defects in innate immune cells. Colitis was abrogated in Nfil3/Il12b double-deficient mice, identifying Il12b dysregulation as a central pathogenic event. Finally, germ-free Nfil3−/− mice do not have colonic inflammation. Thus, NFIL3 is a microbiota-dependent, IL-10-independent regulator of mucosal homeostasis via IL-12p40.
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期刊：
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发表时间：
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期刊：
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