4.8 Article

γδ T cells regulate the intestinal response to nutrient sensing

Journal

SCIENCE
Volume 371, Issue 6535, Pages 1223-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aba8310

Keywords

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Funding

  1. Howard Hughes Medical Institute
  2. NIH [AI144152-01, F32-AI143141, F32-DK125089]
  3. National Science Foundation Graduate Research Fellowship Program [DGE1122492]
  4. National Institute of Diabetes and Digestive and Kidney Diseases [R01DK113375]
  5. International Human Frontier Science Program Organization [LT000037/2018-L]
  6. Jane Coffin Childs Memorial Fund
  7. Blavatnik Family Foundation
  8. Food Allergy Science Initiative

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Research has shown that carbohydrate intake plays a vital role in regulating intestinal epithelial gene expression and the enzymes and transport proteins required for carbohydrate digestion and absorption; gamma delta T cells regulate this process by suppressing interleukin-22 production by type 3 innate lymphoid cells; nutrient availability affects the tissue localization and transcriptome of gamma delta T cells, as well as the cellular remodeling of the epithelial compartment.
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 gamma delta 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 gamma delta T cells. Additionally, transcriptional responses to diet involved cellular remodeling of the epithelial compartment. Thus, this work identifies a role for gamma delta T cells in nutrient sensing.

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