A thermogenic fat-epithelium cell axis regulates intestinal disease tolerance

Kevin Man, Christopher Bowman, Kristina N. Braverman, Veronica Escalante, Yuan Tian, Jordan E. Bisanz, Kirthana Ganeshan, Biao Wang, Andrew Patterson, James R. Bayrer, Peter J. Turnbaugh, Ajay Chawla

Research output: Contribution to journalArticlepeer-review

Abstract

Disease tolerance, the capacity of tissues to withstand damage caused by a stimulus without a decline in host fitness, varies across tissues, environmental conditions, and physiologic states. While disease tolerance is a known strategy of host defense, its role in noninfectious diseases has been understudied. Here, we provide evidence that a thermogenic fat-epithelial cell axis regulates intestinal disease tolerance during experimental colitis. We find that intestinal disease tolerance is a metabolically expensive trait, whose expression is restricted to thermoneutral mice and is not transferable by the microbiota. Instead, disease tolerance is dependent on the adrenergic state of thermogenic adipocytes, which indirectly regulate tolerogenic responses in intestinal epithelial cells. Our work has identified an unexpected mechanism that controls intestinal disease tolerance with implications for colitogenic diseases.

Original languageEnglish (US)
Pages (from-to)32029-32037
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number50
DOIs
StatePublished - Dec 15 2020

All Science Journal Classification (ASJC) codes

  • General

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