A Tissue-intrinsic IL-33/EGF Circuit Promotes Epithelial Regeneration After Intestinal Injury

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Sep 5

PMID 37669929

Authors

Marco Calafiore

Ya-Yuan Fu

Paola Vinci

Viktor Arnhold

Winston Y Chang

Suze A Jansen

Anastasiya Egorova

Shuichiro Takashima

Jason Kuttiyara

Takahiro Ito

Jonathan Serody

Susumu Nakae

Heth Turnquist

Johan van Es

Hans Clevers

Caroline A Lindemans

Bruce R Blazar

Alan M Hanash

Affiliations

Soon will be listed here.

Abstract

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.

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