The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11c^highMHCII⁺ cells (Cnb1 ^CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3⁺ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11c^highMHCII⁺ cells to express IL-2. Deleting IL-2 in CD11c^highMHCII⁺ cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.

中文翻译：

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CD11chighMHCII +髓样细胞产生钙调神经磷酸酶介导的IL-2对于肠道免疫稳态是至关重要的。

肠道免疫系统可以对入侵的病原体做出反应，同时保持对自身抗原和微生物群的免疫耐受性。髓样细胞是这些过程的核心，但是尚不清楚耐受和炎症基础的信号传导途径。在这里，我们显示在CD11c^高MHCII ⁺细胞中缺乏钙调神经磷酸酶B的小鼠（Cnb1 ^CD11c小鼠）自发发展肠道炎症，并容易诱发结肠炎。在这些小鼠中，结肠炎与T型辅助1型（Th1）和Th17细胞群的扩张以及FoxP3 ⁺调节性T（Treg）细胞数量的减少有关，并且病理学与肠Cnb1缺乏症有关。 CD11c^高MHCII ⁺细胞表达IL-2。删除CD11c^高MHCII ⁺细胞中的IL-2会诱发自发性结肠炎，类似于人的炎症性肠病。我们的发现表明，髓样细胞中的钙调神经磷酸酶-NFAT-IL-2途径通过影响小鼠肠道炎症和调节反应的平衡，是肠道稳态的关键调节剂。