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A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance.
Mertens, Randall T; Misra, Aditya; Xiao, Peng; Baek, Seungbyn; Rone, Joseph M; Mangani, Davide; Sivanathan, Kisha N; Arojojoye, Adedamola S; Awuah, Samuel G; Lee, Insuk; Shi, Guo-Ping; Petrova, Boryana; Brook, Jeannette R; Anderson, Ana C; Flavell, Richard A; Kanarek, Naama; Hemberg, Martin; Nowarski, Roni.
Afiliação
  • Mertens RT; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunolo
  • Misra A; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunolo
  • Xiao P; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Baek S; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
  • Rone JM; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunolo
  • Mangani D; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Sivanathan KN; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunolo
  • Arojojoye AS; Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
  • Awuah SG; Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA; Center for Pharmaceutical Research and Innovation, College of Pharmacy and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.
  • Lee I; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea; POSTECH Biotech Center, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
  • Shi GP; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Petrova B; Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Brook JR; Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Anderson AC; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of MIT
  • Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
  • Kanarek N; Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hemberg M; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunolo
  • Nowarski R; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital, and Harvard Medical School, Boston, MA 02115, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Immunolo
Immunity ; 2024 Jun 19.
Article em En | MEDLINE | ID: mdl-38906145
ABSTRACT
Tissues are exposed to diverse inflammatory challenges that shape future inflammatory responses. While cellular metabolism regulates immune function, how metabolism programs and stabilizes immune states within tissues and tunes susceptibility to inflammation is poorly understood. Here, we describe an innate immune metabolic switch that programs long-term intestinal tolerance. Intestinal interleukin-18 (IL-18) stimulation elicited tolerogenic macrophages by preventing their proinflammatory glycolytic polarization via metabolic reprogramming to fatty acid oxidation (FAO). FAO reprogramming was triggered by IL-18 activation of SLC12A3 (NCC), leading to sodium influx, release of mitochondrial DNA, and activation of stimulator of interferon genes (STING). FAO was maintained in macrophages by a bistable switch that encoded memory of IL-18 stimulation and by intercellular positive feedback that sustained the production of macrophage-derived 2'3'-cyclic GMP-AMP (cGAMP) and epithelial-derived IL-18. Thus, a tissue-reinforced metabolic switch encodes durable immune tolerance in the gut and may enable reconstructing compromised immune tolerance in chronic inflammation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article