Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis.

Autor:	Ohishi K; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima, Japan., Dora D; Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary., Han CY; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Guyer RA; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Ohkura T; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Kazimierczyk S; Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Charlestown, MA, USA., Picard N; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Leavitt AR; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Ott LC; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Rahman AA; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Mueller JL; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Shpigel NY; Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel., Jain N; Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Charlestown, MA, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Nagy N; Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary., Hotta R; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Goldstein AM; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Stavely R; Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Inflammatory bowel diseases [Inflamm Bowel Dis] 2024 Aug 05. Date of Electronic Publication: 2024 Aug 05.
DOI:	10.1093/ibd/izae155
Abstrakt:	Background: Immune cell populations in the intestinal muscularis propria during colitis are poorly resolved. Maintaining homeostasis in this niche is critical, highlighted by the poorer prognosis of inflammatory bowel disease associated with muscularis propria inflammation. Methods: This study utilizes single-cell RNA sequencing to survey the immune cell populations within the muscularis propria of normal colon and dextran sodium sulfate-induced colitis. Findings are validated by immunohistochemistry, flow cytometry and cell-lineage tracing in vivo, and in vitro assays with muscularis macrophages (MMφ). Results: In naïve conditions, transcriptional duality is observed in MMφs with 2 major subpopulations: conventional resident Cx3cr1+ MMφs and Lyve1+ MMφs. The Lyve1+ population is phagocytic and expresses several known MMφ markers in mouse and human, confirming their identity as a bona fide MMφ subset. Single-cell transcriptomics indicate that resident MMφs are retained during colitis and exhibit plasticity toward an inflammatory profile. Lyve1+ MMφs, which express anti-inflammatory marker CD163, are absent during colitis, as confirmed by flow cytometry. In contrast, lineage tracing finds that resident Cx3cr1+ MMφs remain during colitis and are not completely replaced by the inflammatory infiltrating monocytes. In vitro studies provide biological evidence of the plasticity of resident Cx3cr1+ MMφs in response to lipopolysaccharide (LPS), mirroring transcriptional observations in vivo of their inflammatory plasticity. Potential markers for colitic MMφs, validated in animal models and in individuals with ulcerative colitis, are identified. Conclusions: Our findings contribute to the understanding of the immune system in the muscularis propria niche during colitis by resolving the heterogeneity and origins of colitic MMφs. (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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