Charles Dinarello and Mihai Netea, theme Infectious diseases and global health and colleagues published in Cell reports that 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, the authors 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.
Related news items

Grants for research on magnesium deficiency and malaria Vidis for Felix Hol and Jeroen de Baaij
1 July 2022 Radboudumc researchers Jeroen de Baaij and Felix Hol both receive an NWO Vidi grant for their research, respectively on magnesium deficiency in type 2 diabetes and on malaria. read more
Field research on malaria vaccine offers unexpected surprise
23 May 2022Field research on the effectiveness of a malaria vaccine, came up with unexpected results for an international group of researchers including Benjamin Mordmüller of Radboudumc. The vaccine evokes a broader response against malaria proteins than there are in the vaccine.
read more
Rubicon grants awarded to three RIMLS researchers
19 April 2022Three researchers have received Rubicon funding from NWO/ZonMw. This will enable Elke Muntjewerff, Laura de Vries and Laurens van de Wiel to do research at a foreign research institute for the next two years.
read more