γδ T cells regulate the intestinal response to nutrient sensing

Zuri A. Sullivan(Yale University), William Khoury-Hanold(Yale University), Jaechul Lim(Yale University), Christopher S. Smillie(Broad Institute), Moshe Biton(Broad Institute), Bernardo Sgarbi Reis(Rockefeller University), Rachel K. Zwick(University of California, San Francisco), Scott D. Pope(Howard Hughes Medical Institute), Kavita Israni-Winger(Yale University), Roham Parsa(Rockefeller University), Naomi H. Philip(Yale University), Saleh Rashed(Yale University), Noah W. Palm(Yale University), Andrew Wang(Yale University), Daniel Mucida(Rockefeller University), Aviv Regev(Broad Institute), Ruslan Medzhitov(Howard Hughes Medical Institute)
Science
March 18, 2021
Cited by 152Open Access
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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.


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