Obesity and obesity-related diseases are at epidemic levels globally (WHO). Obesity-associated inflammation has recently received much attention due to its devastating consequences for many patients suffering from COVID-19. The low levels of chronic inflammation in obesity have led to the updated classification of obesity as an inflammatory disease that results from disturbed metabolic homeostasis. Crosstalk among immune cells and metabolic regulatory cells, such as adipocytes, in the adipose tissue regulate adipose tissue homeostasis. Cell intrinsic and environmental changes can lead to stress and alterations in cytokine production driving an inflammatory response that builds to metabolic decline and development of obesity. Adipose tissue contains populations of tissue-resident immune cells including γδ T cells that produce significant amounts of IL-17A and TNF-α when activated. IL-17 plays roles in regulation of body weight, adipocyte differentiation and insulin and glucose homeostasis. Mice deficient in the JAML protein that is costimulatory for tissue-resident γδ T cells become significantly obese with age compared to wildtype mice with similar food intake. We hypothesize that JAML-CAR interactions play a critical role in regulation of γδ T cell functions to maintain adipose tissue homeostasis. We plan to investigate the mechanism for development of obesity in these mice by looking at direct control of adipocyte differentiation and homeostasis by γδ T cells during development of obesity.