IL-1R1–dependent signaling coordinates epithelial regeneration in response to intestinal damage
| Autor: | David L. Lin, Varun N. Kapoor, Naruhisa Ota, Joseph Chavarria-Smith, Christian Cox, Menno van Lookeren Campagne, Travis W. Bainbridge, Noelyn M. Kljavin, Keith R. Anderson, Joseph R. Arron, Frederic J. de Sauvage, Shannon J. Turley, Yun Li, Søren Warming, Elaine E. Storm, Lifen Wang, Merone Roose-Girma |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Colon Immunology Mice Transgenic Epithelial Damage 03 medical and health sciences 0302 clinical medicine Animals Regeneration Intestinal Mucosa Cells Cultured Receptors Interleukin-1 Type I Chemistry Interleukins Regeneration (biology) Dextran Sulfate Innate lymphoid cell Mesenchymal stem cell Enterobacteriaceae Infections Wnt signaling pathway Epithelial Cells General Medicine Fibroblasts Colitis Intestinal epithelium Coculture Techniques Cell biology Organoids 030104 developmental biology Citrobacter rodentium Stem cell Thrombospondins 030217 neurology & neurosurgery Homeostasis Signal Transduction |
| Zdroj: | Science Immunology. 6 |
| ISSN: | 2470-9468 |
| Popis: | Repair of the intestinal epithelium is tightly regulated to maintain homeostasis. The response after epithelial damage needs to be local and proportional to the insult. How different types of damage are coupled to repair remains incompletely understood. We report that after distinct types of intestinal epithelial damage, IL-1R1 signaling in GREM1+ mesenchymal cells increases production of R-spondin 3 (RSPO3), a Wnt agonist required for intestinal stem cell self-renewal. In parallel, IL-1R1 signaling regulates IL-22 production by innate lymphoid cells and promotes epithelial hyperplasia and regeneration. Although the regulation of both RSPO3 and IL-22 is critical for epithelial recovery from Citrobacter rodentium infection, IL-1R1-dependent RSPO3 production by GREM1+ mesenchymal cells alone is sufficient and required for recovery after dextran sulfate sodium-induced colitis. These data demonstrate how IL-1R1-dependent signaling orchestrates distinct repair programs tailored to the type of injury sustained that are required to restore intestinal epithelial barrier function. |
| Databáze: | OpenAIRE |
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