{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:09:33Z","timestamp":1783706973167,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The chemokine receptor CCR6 guides pathogenic T17 cells, implicated in autoimmune diseases including psoriasis, to sites of inflammation via the chemokine CCL20. Therefor, pharmacological inhibition of CCR6<jats:sup>+<\/jats:sup> immune cell migration provides a novel therapeutic approach. Translatability of such an intervention has not yet been assessed in detail. We evaluated the translatability of the Aldara\u00ae mouse model induced skin inflammation to psoriasis, with particular focus on immune cell trafficking and assessed the efficacy of IDOR\u20101117\u20102520, a highly selective, potent and orally available CCR6 small inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Effects of IDOR\u20101117\u20102520 were investigated in the Aldara\u00ae and IL23 mouse models of skin inflammation using flow cytometry, RNA sequencing and transcriptome\u2010based cell type deconvolution approaches to characterise immune cell migration patterns. These results were compared to human psoriasis transcriptomics data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>IDOR\u20101117\u20102520 dose dependently reduced infiltration of CCR6<jats:sup>+<\/jats:sup> immune cells into inflamed skin, and was equally efficacious as IL\u201017 and IL\u201023 inhibition in models of skin inflammation. Pathway analysis showed molecular similarities in the immune response between human psoriasis and the Aldara\u00ae mouse model. IL\u201017\/IL\u201023 pathway genes were expressed in both human psoriasis and the mouse model. CCR6 inhibition modulated multiple pathways associated with inflammation beyond the proximal IL\u201017\/IL\u201023 pathway. A chemokine\u2013chemokine receptor interaction map implicated CCL20\u2010CCR6 as the dominant axis in recruiting pathogenic T17 cells in both the model\u00a0and in human psoriasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>IDOR\u20101117\u20102520 could provide a promising novel targeted approach to treating psoriasis and, potentially, other autoimmune diseases involving the CCR6\/CCL20 axis and the IL\u201017\/IL\u201023 pathway. IDOR\u20101117\u20102520 is currently being evaluated in a clinical phase 1 trial (ISRCTN28892128).<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70025","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:19:40Z","timestamp":1743394780000},"page":"3452-3475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of IDOR\u20101117\u20102520, a novel, orally available CCR6 antagonist in preclinical models of skin dermatitis"],"prefix":"10.1111","volume":"182","author":[{"given":"Paulina","family":"Kulig","sequence":"first","affiliation":[{"name":"Department of Translational and Pharmacological Science Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pijus","family":"Brazauskas","sequence":"additional","affiliation":[{"name":"Department of Translational and Pharmacological Science Idorsia Pharmaceuticals Ltd  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