Visceral adipose tissue Tregs and the cells that nurture them

Visceral adipose tissue (VAT) is a primary site for storage of excess energy, but it also serves as an important endocrine organ that impacts organismal metabolism. Chronic, low-grade inflammation of VAT, and eventually systemically, is one of the major drivers of obesity-associated insulin resistance and metabolic abnormalities. A unique population of regulatory T cells (Tregs), with a distinct transcriptional profile and antigen receptor repertoire resides in VAT, keeps inflammation in check and regulates organismal metabolism. Accumulation of these cells depends on interactions with other local immunocytes and, importantly, subtypes of VAT mesenchymal stromal cells (VmSCs) that are either immunomodulators or adipogenic. We summarize our current understanding of the phenotype, function, dependencies, derivation, and modulations of VAT Tregs, and review the heterogeneity and regulation of VmSCs as well as their cross talk with VAT Tregs. Lastly, we discuss imperative questions remaining to be answered.