A tissue injury sensing and repair pathway distinct from host pathogen defense.

Autor:	Liu S; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Hur YH; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Cai X; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Cong Q; McDermott Center for Human Growth and Development, Department of Biophysics, and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Yang Y; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Xu C; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Bilate AM; Laboratory of Mucosal Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Gonzales KAU; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Parigi SM; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Cowley CJ; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Hurwitz B; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Luo JD; Bioinformatics Resource Center, The Rockefeller University, New York, NY 10065, USA., Tseng T; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Gur-Cohen S; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Sribour M; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Omelchenko T; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Levorse J; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Pasolli HA; Electron Microscopy Resource Center, The Rockefeller University, New York, NY 10065, USA., Thompson CB; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Mucida D; Laboratory of Mucosal Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA., Fuchs E; Robin Chemers Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2023 May 11; Vol. 186 (10), pp. 2127-2143.e22. Date of Electronic Publication: 2023 Apr 24.
DOI:	10.1016/j.cell.2023.03.031
Abstrakt:	Pathogen infection and tissue injury are universal insults that disrupt homeostasis. Innate immunity senses microbial infections and induces cytokines/chemokines to activate resistance mechanisms. Here, we show that, in contrast to most pathogen-induced cytokines, interleukin-24 (IL-24) is predominately induced by barrier epithelial progenitors after tissue injury and is independent of microbiome or adaptive immunity. Moreover, Il24 ablation in mice impedes not only epidermal proliferation and re-epithelialization but also capillary and fibroblast regeneration within the dermal wound bed. Conversely, ectopic IL-24 induction in the homeostatic epidermis triggers global epithelial-mesenchymal tissue repair responses. Mechanistically, Il24 expression depends upon both epithelial IL24-receptor/STAT3 signaling and hypoxia-stabilized HIF1α, which converge following injury to trigger autocrine and paracrine signaling involving IL-24-mediated receptor signaling and metabolic regulation. Thus, parallel to innate immune sensing of pathogens to resolve infections, epithelial stem cells sense injury signals to orchestrate IL-24-mediated tissue repair. Competing Interests: Declaration of interests S.L. is now an Asst. Prof. in Pharmacology at UT Southwestern Medical Center; X.C. is now an Asst. Prof. in Radiation Oncology at UT Southwestern Medical Center; K.A.U.G. is currently at Novo Nordisk, Research Center, Oxford, England; C.J.C. is now a postdoctoral fellow at NYU; T.T. is now a graduate student at Yale Univ.; B.H. is now a medical student at Weill Cornell Medical College; S.G.-C. is now an Asst. Prof. in Stem Cells and Regenerative Medicine at UCSD; M.S. is now an embryologist at Tennessee Reproductive Medicine in Chattanooga, TN; J.L. is currently at Temple Univ. C.B.T is a founder of Agios Pharmaceuticals. He is on the board of directors of Regeneron and Charles River Laboratories. E.F. is a member of the editorial board of Cell. She is also a former member of the scientific advisory boards of L’Oréal and Arsenal Biosciences and owns stock futures with Arsenal Biosciences. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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