دورية أكاديمية
A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance.
| العنوان: | A metabolic switch orchestrated by IL-18 and the cyclic dinucleotide cGAMP programs intestinal tolerance. |
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| المؤلفون: | 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 Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA., 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 Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., 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 Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA., 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 Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA., 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 and Harvard, Cambridge, MA, USA., 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 Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., 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 Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: rnowarski@bwh.harvard.edu. |
| المصدر: | Immunity [Immunity] 2024 Sep 10; Vol. 57 (9), pp. 2077-2094.e12. Date of Electronic Publication: 2024 Jun 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
| مواضيع طبية MeSH: | Interleukin-18*/metabolism , Interleukin-18*/immunology , Nucleotides, Cyclic*/metabolism , Macrophages*/immunology , Macrophages*/metabolism , Immune Tolerance*, Animals ; Mice ; Humans ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Mice, Knockout ; Fatty Acids/metabolism ; Intestines/immunology ; Immunity, Innate ; Inflammation/immunology ; Inflammation/metabolism ; Glycolysis ; Oxidation-Reduction |
| مستخلص: | 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. Competing Interests: Declaration of interests The authors declare no competing financial interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: IL-18; SLC12A3; bistable circuit; cGAMP; fatty acid oxidation; immunometabolism; intestinal tolerance; macrophage; metabolic reprogramming; metabolic switch |
| المشرفين على المادة: | 0 (Interleukin-18) 0 (Nucleotides, Cyclic) 0 (cyclic guanosine monophosphate-adenosine monophosphate) 0 (Fatty Acids) |
| تواريخ الأحداث: | Date Created: 20240621 Date Completed: 20240911 Latest Revision: 20240919 |
| رمز التحديث: | 20240919 |
| DOI: | 10.1016/j.immuni.2024.06.001 |
| PMID: | 38906145 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4180 |
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| DOI: | 10.1016/j.immuni.2024.06.001 |