{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:52:55Z","timestamp":1789087975208,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100014364","name":"National Children\u2019s Research Centre","doi-asserted-by":"publisher","award":["K\/17\/1"],"award-info":[{"award-number":["K\/17\/1"]}],"id":[{"id":"10.13039\/100014364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","award":["HRA-POR-2015-1066"],"award-info":[{"award-number":["HRA-POR-2015-1066"]}],"id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>SIGIRR has been described as a negative regulator of several IL-1R\/TLR family members and has been implicated in several inflammatory disease conditions. However, it is unknown whether it can suppress IL-36 family cytokines, which are members of the broader IL-1 superfamily that have emerged as critical orchestrators of psoriatic inflammation in both humans and mice. In this study, we demonstrate that SIGIRR is downregulated in psoriatic lesions in humans and mice, and this correlates with increased expression of IL-36 family cytokines. Using Sigirr\u2212\/\u2212 mice, we identify, for the first time (to our knowledge), SIGIRR as a negative regulator of IL-36 responses in the skin. Mechanistically, we identify dendritic cells and keratinocytes as the primary cell subsets in which IL-36 proinflammatory responses are regulated by SIGIRR. Both cell types displayed elevated IL-36 responsiveness in absence of SIGIRR activity, characterized by enhanced expression of neutrophil chemoattractants, leading to increased neutrophil infiltration to the inflamed skin. Blockade of IL-36R signaling ameliorated exacerbated psoriasiform inflammation in Sigirr\u2212\/\u2212 mice and inhibited neutrophil infiltration. These data identify SIGIRR activity as an important regulatory node in suppressing IL-36\u2013dependent psoriatic inflammation in humans and mice.<\/jats:p>","DOI":"10.4049\/jimmunol.2100237","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T15:35:12Z","timestamp":1626104112000},"page":"651-660","source":"Crossref","is-referenced-by-count":20,"title":["SIGIRR Negatively Regulates IL-36\u2013Driven Psoriasiform Inflammation and Neutrophil Infiltration in the Skin"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2321-9219","authenticated-orcid":false,"given":"Eirini","family":"Giannoudaki","sequence":"first","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Stefanska","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7034-121X","authenticated-orcid":false,"given":"Hazel","family":"Lawler","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-9389","authenticated-orcid":false,"given":"Gemma","family":"Leon","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-6656","authenticated-orcid":false,"given":"Yasmina E","family":"Hernandez Santana","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-9795","authenticated-orcid":false,"given":"Najma","family":"Hassan","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane E","family":"Russell","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Horan","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Sweeney","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger S","family":"Preston","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5578-236X","authenticated-orcid":false,"given":"Alberto","family":"Mantovani","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital , Rozzano, Milan ,","place":["Italy"]},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele , Milan ,","place":["Italy"]},{"name":"The William Harvey Research Institute, Queen Mary University , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-7703","authenticated-orcid":false,"given":"Cecilia","family":"Garlanda","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital , Rozzano, Milan ,","place":["Italy"]},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-7293","authenticated-orcid":false,"given":"Padraic G","family":"Fallon","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0130-8766","authenticated-orcid":false,"given":"Patrick T","family":"Walsh","sequence":"additional","affiliation":[{"name":"Trinity Translational Medicine Institute, School of Medicine, Trinity College , Dublin ,","place":["Ireland"]},{"name":"National Children\u2019s Research Centre, Children\u2019s Health Ireland at Crumlin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"2025022608111004600_r1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/nyas.13280","article-title":"The emergence of the IL-36 cytokine family as novel targets for inflammatory diseases","volume":"1417","author":"Walsh","year":"2016","journal-title":"Ann. 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