Gata3 is detrimental to regulatory T cell function in autoimmune diabetes.

Regulatory T cells (Tregs) protect against autoimmunity. In type 1 diabetes (T1D), Tregs slow the progression of beta cell autoimmunity within pancreatic islets. Increasing the potency or frequency of Tregs can prevent diabetes, as evidenced by studies in the nonobese diabetic (NOD) mouse model for T1D. We report herein that a significant proportion of islets Tregs in NOD mice express . The expression of was correlated with the presence of IL-33, a cytokine known to induce and expand Gata3 Tregs. Despite significantly increasing the frequency of Tregs in the pancreas, exogenous IL-33 was not protective. Based on these data, we hypothesized that Gata3 is deleterious to Treg function in autoimmune diabetes. To test this notion, we generated NOD mice with a Treg-specific deletion of . We found that deleting in Tregs strongly protected against diabetes. Disease protection was associated with a shift of islet Tregs toward a suppressive CXCR3Foxp3 population. Our results suggest that islet Gata3 Tregs are maladaptive and that this Treg subpopulation compromises the regulation of islet autoimmunity, contributing to diabetes onset.