Cytokine and metabolic regulation of adipose tissue Tregs

Since their discovery over a decade ago, much has been learned regarding the importance and function of visceral adipose tissue (VAT)-resident regulatory T cells (Tregs). VAT Tregs play a critical role in controlling VAT inflammation and alleviating metabolic disease. However, this population is disrupted in obesity which exacerbates VAT inflammation and metabolic abnormalities. Therefore, understanding the factors governing the accumulation and maintenance of VAT Tregs, both at steady state and under disease conditions, is crucial for identifying the mechanisms underlying obesity-associated metabolic disease and developing novel therapies. Expansion and maintenance of the VAT Treg compartment is strongly influenced by factors in the local tissue microenvironment, including cytokines, T-cell receptor ligands, hormones, and various metabolites. This mini-review will primarily focus on recent advances in our understandings regarding the regulation of mouse epididymal VAT (eVAT) Tregs, which are the most thoroughly characterized VAT Treg population, by tissue microenvironmental factors and cellular metabolic processes. We will also briefly discuss the limited knowledge available regarding the regulation of mouse ovarian VAT (oVAT) Tregs and human omental VAT Tregs, highlight some lingering questions, and provide a prospective view on where the field is heading.