Maf deficiency in T cells dysregulates Treg - TH17 balance leading to spontaneous colitis
Maf deficiency in T cells dysregulates Treg - TH17 balance leading to spontaneous colitis
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DOI：
10.1038/s41598-019-42486-2
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发表时间：
2019-04-16
影响因子：
4.6
通讯作者：
Verdeil, Gregory
中科院分区：
文献类型：
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作者：
Imbratta, Claire;Leblond, Marine M.;Verdeil, Gregory
维持肠道内稳态是免疫系统面临的主要挑战。在这里，我们证明转录因子MAF在T细胞预防胃肠道炎症中起着核心作用。所有T细胞中缺乏Maf的条件敲除小鼠发生自发性晚发性结肠炎，这与FOXP3(+)ROR γ T(+)T细胞比例降低、结肠中IL-10产生抑制和炎性T(H)17细胞增加有关。引人注目的是，FOXP3（+）特异性条件敲除MAF的小鼠没有发生结肠炎，并且在其结肠中显示出正常水平的IL-10，尽管缺乏MAF的调节性T细胞无法抑制用初始CD4(+) T细胞转移的Rag1（-/-）小鼠的结肠炎症。我们发现这些小鼠结肠中IL-10的细胞来源之一是T(H)17细胞。因此，MAF通过调节T-reg和T(H)17细胞之间的平衡，无论是在其分化水平上还是通过调节其功能，都至关重要地参与了肠道稳态的维持。
The maintenance of homeostasis in the gut is a major challenge for the immune system. Here we demonstrate that the transcription factor MAF plays a central role in T cells for the prevention of gastrointestinal inflammation. Conditional knock out mice lacking Maf in all T cells developed spontaneous late-onset colitis, correlating with a decrease of FOXP3(+)ROR gamma t(+)T cells proportion, dampened IL-10 production in the colon and an increase of inflammatory T(H)17 cells. Strikingly, FOXP3(+) specific conditional knock out mice for MAF did not develop colitis and demonstrated normal levels of IL-10 in their colon, despite the incapacity of regulatory T cells lacking MAF to suppress colon inflammation in Rag1(-/-) mice transferred with naive CD4(+) T cells. We showed that one of the cellular sources of IL-10 in the colon of these mice are T(H)17 cells. Thus, MAF is critically involved in the maintenance of the gut homeostasis by regulating the balance between T-reg and T(H)17 cells either at the level of their differentiation or through the modulation of their functions.