Requirement of mitochondrial transcription factor A in interleukin-17-producing gdT cells to regulate the small intestine homeostasis and metabolism
Interleukin 17 (IL-17)-producing gamma delta T (gdT17) cells are one of the major cellular sources of IL-17 under the steady state and in disease. However, gdT17 cell metabolism and its role in tissue homeostasis remain poorly understood. Here, we show that the tissue milieu shapes splenic and intestinal gdT17 cell gene signatures. Conditional deletion of mitochondrial transcription factor A (Tfam) in gdT17 cells significantly affected gdT17 cell maintenance systemically. In vivo deletion of Tfam in gdT17 cells resulted in small intestinal tissue remodeling and increased small intestine length that was caused by the enhanced tuft cell–group 2 innate lymphoid cell (ILC2) circuit in mice. In vitro, IL-22, a cytokine highly produced by gdT17 cells, inhibited IL-13-induced tuft cell differentiation. Mice with Tfam deletion in gdT17 cells also showed dysregulation of the small intestine transcriptome and metabolism with less body weight but enhanced anti-helminth immunity. Thus, our work revealed a critical role of mitochondrial metabolism in gdT17 cell maintenance and in regulating small intestine homeostasis and metabolism. Overall design: RNA-seq (3 replicates) analysis of spleeen, small intestine, and large intestine gdT17 cells from Tfam cKO and control mice as well as (3 replicates) analysis of small intestine tissue from Tfam cKO and control mice