γδ T Cells and diet-induced inflammation in adipose tissue (173.2)

Abstract Adipose tissues contain several subsets of immune cells. Relatively little is known about their contributions to adipose tissue inflammation induced by feeding mice a diet rich in saturated fats. Using a model of diet-induced obesity in male C57BL/6J mice, we investigated the possible contributions of γδ T cells to this inflammation. γδ T cells make up about one-third of the total T cell population in the epididymal adipose tissue. The γδ T cell receptor was blocked in wild-type mice using an anti-TCRδ antibody. A decrease in macrophage marker F4/80 was observed in these mice as compared to saline-treated control mice on high fat diet (HFD). TCRδ-/- mice adipose tissue failed to show an increase in mRNA expression of cytokines such as CCL-2, IL-6, IFN- γ even though they ate similar amounts of food and showed similar weight gain pattern as wild-type mice. A fraction of adipose tissue γδ T cells were shown to produce IFN-γ in obese mice by flow cytometry and were CD27+, a marker for IFN-γ-producing γδ T cells in the periphery. Obesity also results in inflammation in the skeletal muscle and liver, along with adipose tissue inflammation. Obese TCRδ-/- mice have reduced expression of markers of inflammation in the muscle after 5 weeks on HFD and liver after 6 months on HFD as compared to wild-type mice. These results are consistent with the conclusion that adipose tissue, liver and skeletal muscle inflammation during high saturated fat feeding is dependent in part on γδ T cells.