In recent years, the importance of innate-like lymphocytes in adipose tissue homeostasis and their ability to modulate severity of obesity-induced insulin resistance has emerged. Although eosinophils, ILC2s, NK, and NKT cells in the adipose tissue have been functionally characterized, the role of γδ T cells in the adipose tissue remains unknown. Their ability to produce inflammatory cytokines that correlate with worsening insulin sensitivity, such as TNFα and IL-17, suggest that γδ T cells may be pathogenic during obesity. Indeed, we find that TCRδ KO mice are protected from insulin resistance after both short- and long-term high fat diet feeding despite similar increases in body weight. These γδ T cells are found at the highest frequency in the adipose tissue compared to elsewhere in the body. Furthermore, using parabiotic mice we find that this population uniquely resides in the adipose tissue and minimally recirculates. In order to better understand the mechanism by which γδ T cells are pathogenic during diet-induced obesity, we phenotyped the adipose tissue γδ T cells using a panel of transcription factors and surface markers originally employed to study thymic γδ T cells as part of the Immunological Genome Consortium. Additionally through low-input RNA-seq and single-cell TCR sequencing, we uncovered two phenotypically and functionally discrete populations of γδ T cells based on gene expression, cytokine profiles, and TCR repertoires. Although efforts to fully elucidate the unique enrichment, phenotype, and function of γδ T cells in the adipose tissue and their dysbiosis during obesity-induced insulin resistance are on-going, our preliminary results strengthen a case for the importance of γδ T cells in the adipose tissue and promise further elucidation of their key functions in peripheral tissue sites.  

This work is supported by: NIH Training Grant T32 AR07530