Insights into the multifaceted role of interleukin-37 on human immune cell regulation

• Published in: Clinical immunology (Orlando, Fla.) Vol. 268; p. 110368
• Main Authors: Teufel, Lisa U., Matzaraki, Vasiliki, Folkman, Lukas, ter Horst, Rob, Moorlag, Simone J.C.F.M., Mulders-Manders, Catharina M., Netea, Mihai G., Krausgruber, Thomas, Joosten, Leo A.B., Arts, Rob J.W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2024
• Subjects: Autoinflammation; BCG; Inflammation; Interleukin (IL)-37; Trained immunity; Interleukin (IL)-37; Inflammation; Trained immunity; Autoinflammation; BCG
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110368

Autoinflammatory diseases, while having a variety of underlying causes, are mediated by dysfunctional innate immune responses. Therefore, standard treatments target innate cytokines or block their receptors. Despite excellent responses in some patients, first-line treatments fail in others, for reasons which remain to be understood. We studied the effects of IL-37, an anti-inflammatory cytokine, on immune cells using multi-omics profiling of 325 healthy adults. Our findings show that IL-37 is associated with inflammation control and generally reduced immune cell activity. Further, genetic variants in IL37 are associated with impaired trained immunity, a memory phenotype of innate immune cells contributing to autoinflammation. To underpin the medical potential of IL-37, an explorative cohort of seven autoinflammatory disorders was built. In vitro stimulation experiments argue for recombinant IL-37 as a potential therapy in IL-6-, and IL-22-driven conditions. Concluding, IL-37 is highlighted as a cytokine with broad anti-inflammatory functions, implicating its potential as therapeutic intervention. [Display omitted] •The induction of trained immunity in humans can be regulated by IL-37 in vivo.•IL-37 is a potential therapeutic in inflammatory conditions.•IL-37 regulates cellular activity, effector functions, and inflammation in humans.•IL-37 controls lipid, fatty acid, and amino acid metabolism.