Role of IL-17A-Producing γδ T Cells in Regulating Non-Shivering Thermogenesis in the Adipose Tissue

Abstract

γδ T cells are innate-like T cells that mediate host defense functions through the production of chemokines and cytokines. Distinct subsets of these cells, identified by gamma chains of their T cell receptor, have been found to display different functions across various anatomical locations. Although recent findings point to an enriched population of Vγ4/6 subset in the adipose tissue, little is known about the function of these populations. According to recent results, mice deficient in γδ T cells display the inability to regulate core body temperature upon cold challenge, due to impaired uncoupling protein 1 (UCP-1) dependent adaptive thermogenesis in the adipose tissue. Because this population of γδ T cells has been found to be potent producers of IL-17A upon stimulation with PMA and ionomycin, we hypothesize that IL-17A plays a critical role in the regulation of adaptive thermogenesis. Using γδ T cell- and IL-17A-deficient mice, we observe how thermogenesis, lipolysis, and neurotransmission are affected at the protein and transcriptional level. We find that IL-17A-/- mice fail to upregulate thermogenic genes, most notably Ucp1, Dio2, and Ppargc1a. These mice also display a decreased expression of the lipase genes Hsl and Atgl as well as reduced activation of the coded enzymes, indicated by a lower degree of phosphorylation. Furthermore, mice deficient in IL-17A show a reduced expression of the gene coding for beta adrenergic receptor 3 (Adrb3) in the adipose tissue, suggesting a reduced sensitivity towards catecholamine signaling. Together, these results highlight the importance of IL-17A-producing γδ T cells within the adipose tissue for the maintenance of core body temperature through adaptive, non-shivering thermogenesis.