Metabolic regulation of γδintraepithelial lymphocytes

Abstract

Elucidating the relationship between cellular metabolism and T cell function has substantially advanced our understanding of how T cells are regulated in response to activation. The metabolic profiles of circulating or peripheral T cells have been well-described, yet less is known regarding how complex local microenvironments shape or modulate the bioenergetic profile of tissue-resident T lymphocytes. Intraepithelial lymphocytes expressing the γδT cell receptor (γδIELs) provide immunosurveillance of the intestinal epithelium to limit tissue injury and microbial invasion; however, their activation and effector responses occur independently of antigen recognition. In this review, we will summarize the current knowledge regarding γδT cell and IEL metabolic profiles and how this informs our understanding of γδIEL metabolism. We will also discuss the role of the gut microbiota in shaping the metabolic profile of these sentinel lymphocytes, and in turn, how these bioenergetics contribute to regulation of γδIEL surveillance behavior and effector function. Improved understanding of the metabolic processes involved in γδIEL homeostasis and function may yield novel strategies to amplify the protective functions of these cells in the context of intestinal health and disease.