Expression of the miR‐17~92a cluster of microRNAs by regulatory T cells controls blood glucose homeostasis

Abstract

AbstractRegulatory T cells (Tregs) are a specialized immune cell type that play important roles in regulating immune responses. However, those found in adipose tissue, particularly visceral adipose tissue (VAT), have also been shown to exert metabolic regulatory functions. This study investigated the requirement of the miR‐17~92a cluster of microRNAs in VAT Tregs and the impact on blood glucose. This cluster of microRNAs is one that we previously showed to be important for the fitness of Tregs found in secondary lymphoid organs. It was found that male mice with Treg‐specific miR‐17~92a deficiency are resistant to impaired glucose tolerance induced by a high‐fat diet. However, high‐fat feeding still impaired glucose tolerance in female mice with Treg‐specific miR‐17~92a deficiency. There was an increase in KLRG1− naïve Tregs and a loss of KLRG1+ terminally differentiated Tregs in the VAT of Treg‐specific miR‐17~92a‐deficient male mice but not in female mice. The protection of male mice from high‐fat feeding was also associated with increased interleukin‐10 and reduced interferonγ expression by conventional CD4+ T cells and reduced interleukin‐2 expression by both CD4+ and CD8+ T cells in the VAT. Together this suggests that expression of miR‐17~92a by VAT Tregs regulates the effector phenotype of conventional T cells and in turn the metabolic function of adipose tissue and blood glucose homeostasis.