{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:44:30Z","timestamp":1790729070718,"version":"4.1.0"},"reference-count":137,"publisher":"Portland Press Ltd.","issue":"4","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,28]]},"abstract":"<jats:p>Interleukin-36 (IL-36) cytokines are structurally similar to other Interleukin-1 superfamily members and are essential to convey inflammatory responses at epithelial barriers including the skin, lung, and gut. Due to their potent effects on immune cells, IL-36 cytokine activation is regulated on multiple levels, from expression and activation to receptor binding. Different IL-36 isoforms convey specific responses as a consequence of particular danger- or pathogen-associated molecular patterns. IL-36 expression and activation are regulated by exogenous pathogens, including fungi, viruses and bacteria but also by endogenous factors such as antimicrobial peptides or cytokines. Processing of IL-36 into potent bioactive forms is necessary for host protection but can elevate tissue damage. Indeed, exacerbated IL-36 signalling and hyperactivation are linked to the pathogenesis of diseases such as plaque and pustular psoriasis, emphasising the importance of understanding the molecular aspects regulating IL-36 activation. Here, we summarise facets of the electrochemical properties, regulation of extracellular cleavage by various proteases and receptor signalling of the pro-inflammatory and anti-inflammatory IL-36 family members. Additionally, this intriguing cytokine subfamily displays many characteristics that are unique from prototypical members of the IL-1 family and these key distinctions are outlined here.<\/jats:p>","DOI":"10.1042\/bst20230548","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T14:19:54Z","timestamp":1721398794000},"page":"1591-1604","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular aspects of Interleukin-36 cytokine activation and regulation"],"prefix":"10.1042","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0417-4237","authenticated-orcid":false,"given":"Jennifer","family":"Keller","sequence":"first","affiliation":[{"name":"1Department of Dermatology, University Hospital Z\u00fcrich (USZ), University of Z\u00fcrich (UZH), Raemistrasse 100, 8091 Z\u00fcrich, Switzerland"},{"name":"2Faculty of Science, University of Z\u00fcrich, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-8292","authenticated-orcid":false,"given":"James R.","family":"O\u2019 Siorain","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, University Hospital Z\u00fcrich (USZ), University of Z\u00fcrich (UZH), Raemistrasse 100, 8091 Z\u00fcrich, Switzerland"},{"name":"3Faculty of Medicine, University of Z\u00fcrich, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-8766","authenticated-orcid":false,"given":"Thomas M.","family":"K\u00fcndig","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, University Hospital Z\u00fcrich (USZ), University of Z\u00fcrich (UZH), Raemistrasse 100, 8091 Z\u00fcrich, Switzerland"},{"name":"3Faculty of Medicine, University of Z\u00fcrich, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6315-167X","authenticated-orcid":false,"given":"Mark","family":"Mellett","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, University Hospital Z\u00fcrich (USZ), University of Z\u00fcrich (UZH), Raemistrasse 100, 8091 Z\u00fcrich, Switzerland"},{"name":"3Faculty of Medicine, University of Z\u00fcrich, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"2024082813205788800_BST-2023-0548CC1","doi-asserted-by":"publisher","first-page":"808012","DOI":"10.3389\/fimmu.2021.808012","article-title":"The immunological impact of IL-1 family cytokines on the epidermal barrier","volume":"12","year":"2021","journal-title":"Front. 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