Maf deficiency in T cells dysregulates T_reg - T_H17 balance leading to spontaneous colitis.

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 gastro-intestinal inflammation. Conditional knock out mice lacking Maf in all T cells developed spontaneous late-onset colitis, correlating with a decrease of FOXP3⁺RORγt⁺ T cells proportion, dampened IL-10 production in the colon and an increase of inflammatory T_H17 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 naïve CD4⁺ T cells. We showed that one of the cellular sources of IL-10 in the colon of these mice are T_H17 cells. Thus, MAF is critically involved in the maintenance of the gut homeostasis by regulating the balance between T_reg and T_H17 cells either at the level of their differentiation or through the modulation of their functions.

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