Interleukin-37 signaling

Interleukins (IL) are immunomodulatory proteins that elicit a wide array of responses in cells and tissues. Interleukin 37 (IL37), also known as IL 1F7, is a member of the IL 1 family. Isoform b of IL37 (referred just as IL37) is synthesized as a precursor that requires processing (primarily by caspase 1) to attain full receptor agonist or antagonist function. Both full length and processed IL37 can bind to the IL 18 binding protein (IL 18BP) and the Interleukin 18 receptor 1 (IL 18R1). Upon binding to the IL18R1, IL37 recruits Single Ig IL 1 related receptor (SIGIRR). The IL37:IL18R1 complex can activate phosphorylation of Signal transducer and activator of transcription 3 (STAT3), Tyrosine protein kinase Mer and Phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase and dual specificity protein phosphatase PTEN and can also inhibit Nuclear factor NF kappa B p105 subunit (NFKB). Processed IL37 can be secreted from the cytosol to the extracellular space or translocated into the nucleus. Full length IL37 can also be secreted from the cytosol to the extracellular space. Processed IL37 can bind with Mothers against decapentaplegic homolog 3 (SMAD3) in the cytosol and then translocate to the nucleus, where it facilitates transcription of Tyrosine protein phosphatase non receptors (PTPNs). These events ultimately lead to suppression of cytokine production in several types of immune cells resulting in reduced inflammation.

Summary from Reactome (R-HSA-9008059), read 2026-09-23.