The Autophagy Gene Atg16i1 Differentially Regulates T-Reg And T(H)2 Cells To Control Intestinal Inflammation

A polymorphism in the autophagy gene Atg1611 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4(+) T cell responses in the intestine. Selective deletion of Atg1611 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3(+) T-reg cells. Specific ablation of Atg1611 in Foxp3(+) T-reg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal T(H)2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal T-H cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders.