gd T-cells regulate transcriptional response to diet in the intestinal epithelium

As a site of direct encounter with the external environment, the intestine must balance nutrient uptake with barrier defense. This requires coordination between numerous cell types that engage whole tissue responses to changes in environmental variables. To investigate how nutrient uptake is regulated in the small intestine, we tested the effects of diets with different macronutrient composition on epithelial cell gene expression. We found that expression of enzymes and transporters required for digestion and absorption of carbohydrates, but not protein, was dependent on substrate availability. Surprisingly, the 'on-demand' induction of this machinery required gd Tcells, which regulated this program via suppression of IL-22 expression by ILC3s. We found that nutrient availability alters the tissue localization and transcriptome of gd T-cells and that transcriptional responses to diet involved cellular remodeling of the epithelial compartment. This work thus identified a novel role of intestinal gd T-cells in nutrient sensing. Overall design: Bulk RNA-seq of intestinal epithelial cells, gd T cells, and ab T cells from mice fed with high carb or high protein diet, respectively.