{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T18:29:24Z","timestamp":1776882564811,"version":"3.51.2"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Several types of psoriasiform dermatitis are associated with increased IL-36 cytokine activity in the skin. A rare, but severe, psoriasis-like disorder, generalized pustular psoriasis (GPP), is linked to loss-of-function mutations in the gene encoding IL-36RA, an important negative regulator of IL-36 signaling. To understand the effects of IL-36 dysregulation in a mouse model, we studied skin inflammation induced by intradermal injections of preactivated IL-36\u03b1. We found the immune cells infiltrating IL-36\u03b1\u2013injected mouse skin to be of dramatically different composition than those infiltrating imiquimod-treated skin. The IL-36\u03b1\u2013induced leukocyte population comprised nearly equal numbers of CD4+ \u03b1\u03b2 T cells, neutrophils, and inflammatory dendritic cells, whereas the imiquimod-induced population comprised \u03b3\u03b4 T cells and neutrophils. Ligands for chemokine receptors CCR6 and CXCR2 are increased in both GPP and IL-36\u03b1\u2013treated skin, which led us to test an optimized small-molecule antagonist (CCX624) targeting CCR6 and CXCR2 in the IL-36\u03b1 model. CCX624 significantly reduced the T cell, neutrophil, and inflammatory dendritic cell infiltrates and was more effective than saturating levels of an anti\u2013IL-17RA mAb at reducing inflammatory symptoms. These findings put CCR6 and CXCR2 forward as novel targets for a mechanistically distinct therapeutic approach for inflammatory skin diseases involving dysregulated IL-36 signaling, such as GPP.<\/jats:p>","DOI":"10.4049\/jimmunol.1801519","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T20:29:23Z","timestamp":1549312163000},"page":"1687-1692","source":"Crossref","is-referenced-by-count":25,"title":["Efficacy of Chemokine Receptor Inhibition in Treating IL-36\u03b1\u2013Induced Psoriasiform Inflammation"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4252-5182","authenticated-orcid":false,"given":"James J","family":"Campbell","sequence":"first","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-6947","authenticated-orcid":false,"given":"Karen","family":"Ebsworth","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda S","family":"Ertl","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey P","family":"McMahon","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Yau","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkat R","family":"Mali","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky","family":"Chhina","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0618-6582","authenticated-orcid":false,"given":"Alice","family":"Kumamoto","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley","family":"Liu","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0035-2746","authenticated-orcid":false,"given":"Ton","family":"Dang","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale","family":"Newland","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel F","family":"Charo","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penglie","family":"Zhang","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J","family":"Schall","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajinder","family":"Singh","sequence":"additional","affiliation":[{"name":"ChemoCentryx, Inc. , Mountain View, CA 94043"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"2025030417560988300_r1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3389\/fimmu.2018.00200","article-title":"IL-36\u03b3 is a strong inducer of IL-23 in psoriatic cells and activates angiogenesis","volume":"9","author":"Bridgewood","year":"2018","journal-title":"Front. Immunol."},{"key":"2025030417560988300_r2","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.4049\/jimmunol.1301481","article-title":"IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin","volume":"192","author":"Foster","year":"2014","journal-title":"J. Immunol."},{"key":"2025030417560988300_r3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2340\/00015555-2808","article-title":"Highlighting interleukin-36 signalling in plaque psoriasis and pustular psoriasis","volume":"98","author":"Furue","year":"2018","journal-title":"Acta Derm. Venereol."},{"key":"2025030417560988300_r4","doi-asserted-by":"crossref","first-page":"42594","DOI":"10.1074\/jbc.M111.267922","article-title":"Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36\u03b1, IL-36\u03b2, and IL-36\u03b3) or antagonist (IL-36Ra) activity","volume":"286","author":"Towne","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2025030417560988300_r5","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1056\/NEJMoa1013068","article-title":"Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis","volume":"365","author":"Marrakchi","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2025030417560988300_r6","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ajhg.2011.07.022","article-title":"Mutations in IL36RN\/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis","volume":"89","author":"Onoufriadis","year":"2011","journal-title":"Am. J. Hum. 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Dermatol."},{"key":"2025030417560988300_r10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00281-015-0539-8","article-title":"Update on psoriasis immunopathogenesis and targeted immunotherapy","volume":"38","author":"Mahil","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"2025030417560988300_r11","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1111\/jdv.14386","article-title":"European consensus statement on phenotypes of pustular psoriasis","volume":"31","author":"Navarini","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"2025030417560988300_r12","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.4049\/jimmunol.1700826","article-title":"IL-17-secreting \u03b3\u03b4 T cells are completely dependent upon CCR6 for homing to inflamed skin","volume":"199","author":"Campbell","year":"2017","journal-title":"J. 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Dermatol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/202\/6\/1687\/61417500\/ji1801519.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/202\/6\/1687\/61417500\/ji1801519.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T20:03:40Z","timestamp":1741118620000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/202\/6\/1687\/7952137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,3,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1801519","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2019,3]]}}}