{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:45:29Z","timestamp":1788954329467,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36\u2014a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs\u2014a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.<\/jats:p>","DOI":"10.3390\/ijms22158076","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T11:12:52Z","timestamp":1627470772000},"page":"8076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-4924","authenticated-orcid":false,"given":"Pio","family":"Conti","sequence":"first","affiliation":[{"name":"Postgraduate Medical School, University of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3919-0679","authenticated-orcid":false,"given":"Fabrizio E.","family":"Pregliasco","sequence":"additional","affiliation":[{"name":"Istituto Ortopedico Galeazzi, 20100 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa G.","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Facolt\u00e0 di Scienze dell\u2019Educazione Motoria, Universit\u00e0 \u201cCarlo Bo\u201d, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8603","authenticated-orcid":false,"given":"Carla E.","family":"Gallenga","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Specialist Surgery, University of Ferrara, 44100 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Caraffa","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros K.","family":"Kritas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Aristotle University of Thessaloniki, 54250 Macedonia, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3550-1812","authenticated-orcid":false,"given":"Dorina","family":"Lauritano","sequence":"additional","affiliation":[{"name":"Medicine and Surgery Centre of Neuroscience of Milan, University of Milan-Bicocca, 20100 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaolo","family":"Ronconi","sequence":"additional","affiliation":[{"name":"Clinica dei Pazienti del Territorio, Fondazione Policlinico Gemelli, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1073\/pnas.1000803107","article-title":"IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin","volume":"107","author":"Theoharides","year":"2010","journal-title":"Proc. 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