γδ T cells regulate the intestinal response to nutrient sensing

Science. 2021 Mar 19;371(6535):eaba8310. doi: 10.1126/science.aba8310.

Abstract

The intestine is a site of direct encounter with the external environment and must consequently balance barrier defense with nutrient uptake. To investigate how nutrient uptake is regulated in the small intestine, we tested the effect of diets with different macronutrient compositions on epithelial gene expression. We found that enzymes and transporters required for carbohydrate digestion and absorption were regulated by carbohydrate availability. The "on-demand" induction of this machinery required γδ T cells, which regulated this program through the suppression of interleukin-22 production by type 3 innate lymphoid cells. Nutrient availability altered the tissue localization and transcriptome of γδ T cells. Additionally, transcriptional responses to diet involved cellular remodeling of the epithelial compartment. Thus, this work identifies a role for γδ T cells in nutrient sensing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Communication
  • Dietary Carbohydrates / administration & dosage*
  • Dietary Carbohydrates / metabolism*
  • Dietary Proteins / administration & dosage
  • Digestion
  • Enterocytes / physiology*
  • Gene Expression Regulation
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Intestinal Absorption
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / physiology*
  • Intestine, Small / cytology
  • Intestine, Small / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nutrients / administration & dosage
  • Nutrients / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology*
  • Transcription, Genetic
  • Transcriptome

Substances

  • Dietary Carbohydrates
  • Dietary Proteins
  • Interleukins
  • Receptors, Antigen, T-Cell, gamma-delta