The IL-10 receptor inhibits cell extrinsic signals necessary for STAT1-dependent macrophage accumulation during colitis.

Autor:	Patik I; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA., Redhu NS; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA; Morphic Therapeutic, Waltham, Massachusetts, USA., Eran A; Computational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts, USA., Bao B; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA., Nandy A; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA., Tang Y; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA., El Sayed S; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, Department of Microbiology, Zagazig University, Zagazig, Ash Sharkia, Egypt., Shen Z; Division of Comparative Medicine, Massachusetts Institute of Technology, Massachusetts, USA., Glickman J; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Fox JG; Division of Comparative Medicine, Massachusetts Institute of Technology, Massachusetts, USA., Snapper SB; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA., Horwitz BH; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA; Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts, USA. Electronic address: Bruce.Horwitz@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	Mucosal immunology [Mucosal Immunol] 2023 Jun; Vol. 16 (3), pp. 233-249. Date of Electronic Publication: 2023 Mar 02.
DOI:	10.1016/j.mucimm.2023.02.006
Abstrakt:	The loss of IL-10R function leads to severe early onset colitis and, in murine models, is associated with the accumulation of immature inflammatory colonic macrophages. We have shown that IL-10R-deficient colonic macrophages exhibit increased STAT1-dependent gene expression, suggesting that IL-10R-mediated inhibition of STAT1 signaling in newly recruited colonic macrophages might interfere with the development of an inflammatory phenotype. Indeed, STAT1 -/- mice exhibit defects in colonic macrophage accumulation after Helicobacter hepaticus infection and IL-10R blockade, and this was phenocopied in mice lacking IFNγR, an inducer of STAT1 activation. Radiation chimeras demonstrated that reduced accumulation of STAT1-deficient macrophages was based on a cell-intrinsic defect. Unexpectedly, mixed radiation chimeras generated with both wild-type and IL-10R-deficient bone marrow indicated that rather than directly interfering with STAT1 function, IL-10R inhibits the generation of cell extrinsic signals that promote the accumulation of immature macrophages. These results define the essential mechanisms controlling the inflammatory macrophage accumulation in inflammatory bowel diseases. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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