Journal
CELL REPORTS
Volume 35, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.108955
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Funding
- AIRC under MFAG 2018 [22136]
- FOREUM (Career Award 2020)
- Interleukin Foundation
- Netherlands Organization for Scientific Research (VENI grant) [09150161810007]
- Netherlands Organization for Scientific Research (Spinoza grant)
- NIH [AI-15614]
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Trained immunity is an innate immune memory program induced by exposure to pathogens or vaccines, evolved as protection against infections. IL-37 suppresses the effects of TI by reversing immunometabolic changes and inhibiting specific cellular responses.
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.
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