The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity.
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.
['Cavalli|Giulio|G|', 'Tengesdal|Isak W|IW|', 'Gresnigt|Mark|M|', 'Nemkov|Travis|T|', 'Arts|Rob J W|RJW|', 'Domínguez-Andrés|Jorge|J|', 'Molteni|Raffaella|R|', 'Stefanoni|Davide|D|', 'Cantoni|Eleonora|E|', 'Cassina|Laura|L|', 'Giugliano|Silvia|S|', 'Schraa|Kiki|K|', 'Mills|Taylor S|TS|', 'Pietras|Eric M|EM|', 'Eisenmensser|Elan Z|EZ|', 'Dagna|Lorenzo|L|', 'Boletta|Alessandra|A|', "D'Alessandro|Angelo|A|", 'Joosten|Leo A B|LAB|', 'Netea|Mihai G|MG|', 'Dinarello|Charles A|CA|']
cytokines trained immunity innate immunity infection immunometabolism inflammation IL-1 family cell energy metabolism epigenetics neutrophils regulatory cytokine