The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity.

Autor:	Cavalli G; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA; Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy., Tengesdal IW; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA., Gresnigt M; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany., Nemkov T; Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80045, USA., Arts RJW; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Domínguez-Andrés J; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Molteni R; Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Stefanoni D; Vita-Salute San Raffaele University, Milan, Italy., Cantoni E; Vita-Salute San Raffaele University, Milan, Italy., Cassina L; Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Giugliano S; Laboratory of Mucosal Immunology and Microbiota, Humanitas Clinical and Research Center - IRCCS, via Manzoni 56, 20089 Rozzano (MI), Italy., Schraa K; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Mills TS; Division of Hematology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA., Pietras EM; Division of Hematology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA., Eisenmensser EZ; Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80045, USA., Dagna L; Vita-Salute San Raffaele University, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy., Boletta A; Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy., D'Alessandro A; Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80045, USA., Joosten LAB; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands., Netea MG; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Dinarello CA; Department of Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: cdinare333@aol.com.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Apr 06; Vol. 35 (1), pp. 108955.
DOI:	10.1016/j.celrep.2021.108955
Abstrakt:	Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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