Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells.

Autor:	Jacobse J; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA., Brown RE; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Li J; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Pilat JM; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA., Pham L; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Short SP; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Peek CT; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Rolong A; Department of Cell and Developmental Biology and Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Washington MK; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Martinez-Barricarte R; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA., Byndloss MX; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA., Shelton C; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Markle JG; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA., Latour YL; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Allaman MM; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA., Cassat JE; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, USA., Wilson KT; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA., Choksi YA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Williams CS; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA., Lau KS; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology and Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Flynn CR; Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France; The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY, USA; Howard Hughes Medical Institute, New York, NY, USA., Rings EHHM; Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands; Sophia Children's Hospital, Department of Pediatrics, Erasmus University, Erasmus University Medical Center, Rotterdam, the Netherlands., Samsom JN; Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center, Rotterdam, the Netherlands., Goettel JA; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, 1075J MRB IV, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: jeremy.goettel@vumc.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112128. Date of Electronic Publication: 2023 Feb 17.
DOI:	10.1016/j.celrep.2023.112128
Abstrakt:	The cytokine interleukin-23 (IL-23) is involved in the pathogenesis of inflammatory and autoimmune conditions including inflammatory bowel disease (IBD). IL23R is enriched in intestinal Tregs, yet whether IL-23 modulates intestinal Tregs remains unknown. Here, investigating IL-23R signaling in Tregs specifically, we show that colonic Tregs highly express Il23r compared with Tregs from other compartments and their frequency is reduced upon IL-23 administration and impairs Treg suppressive function. Similarly, colonic Treg frequency is increased in mice lacking Il23r specifically in Tregs and exhibits a competitive advantage over IL-23R-sufficient Tregs during inflammation. Finally, IL-23 antagonizes liver X receptor pathway, cellular cholesterol transporter Abca1, and increases Treg apoptosis. Our results show that IL-23R signaling regulates intestinal Tregs by increasing cell turnover, antagonizing suppression, and decreasing cholesterol efflux. These results suggest that IL-23 negatively regulates Tregs in the intestine with potential implications for promoting chronic inflammation in patients with IBD. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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