Interleukin-37 signaling

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R-HSA-9008059
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Homo sapiens
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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 (Sharma et al. 2008). 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 (Kumar et al. 2002). Both full length and processed IL37 can bind to the IL 18 binding protein (IL 18BP) and the Interleukin 18 receptor 1 (IL 18R1) (Shi et al. 2003). Upon binding to the IL18R1, IL37 recruits Single Ig IL 1 related receptor (SIGIRR) (Nold-Petry et al. 2015). 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) (Nold-Petry et al. 2015). Processed IL37 can be secreted from the cytosol to the extracellular space or translocated into the nucleus (Bulau et al. 2014). Full length IL37 can also be secreted from the cytosol to the extracellular space (Bulau et al. 2014). 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) (Nold et al. 2010, Luo et al. 2017). These events ultimately lead to suppression of cytokine production in several types of immune cells resulting in reduced inflammation.

Literature References
PubMed ID Title Journal Year
28548248 The emerging role of interleukin-37 in cardiovascular diseases

Zhuang, X, Wu, B, Li, J, Shi, H, Jin, B, Luo, X

Immun Inflamm Dis 2017
22047735 IL-37: a new anti-inflammatory cytokine of the IL-1 family

Boraschi, D, Lucchesi, D, Hainzl, S, Leitner, M, Maier, E, Mangelberger, D, Oostingh, GJ, Pfaller, T, Pixner, C, Posselt, G, Italiani, P, Nold, MF, Nold-Petry, CA, Bufler, P, Dinarello, CA

Eur. Cytokine Netw. 2011
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