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In contrast, poorly responsive patients were distinguished by persistent activation of IL-17\u2013producing T (T17) cells, a mechanism distinct from alternative cytokine signaling or resistance isolated to epidermal keratinocytes. Even in IL-23 blockade\u2013responsive patients, we detected a recurring set of recalcitrant, disease-specific transcriptional abnormalities. This irreversible immunological state may necessitate ongoing IL-23 inhibition. Spatial transcriptomic analyses also suggested that successful IL-23 blockade requires dampening of &gt;90% of IL-17\u2013induced response in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. Collectively, our data establish a patient-level paradigm for dissecting responses to immunomodulatory treatments.<\/jats:p>","DOI":"10.1126\/sciimmunol.adi2848","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T13:59:11Z","timestamp":1706277551000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":47,"title":["A single-cell atlas of IL-23 inhibition in cutaneous psoriasis distinguishes clinical response"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-3667","authenticated-orcid":true,"given":"David","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-2543","authenticated-orcid":true,"given":"Ashley A.","family":"Hailer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA."},{"name":"Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA 94121, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9881-4290","authenticated-orcid":true,"given":"Sijia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA."},{"name":"Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA 94121, USA."},{"name":"Department of Dermatology, Second Affiliated Hospital, School of Medicine, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Chan","sequence":"additional","affiliation":[{"name":"Dermatopathology Service, University of California, San Francisco, San Francisco, CA 94107, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8321-4025","authenticated-orcid":true,"given":"Abdullah","family":"El Kurdi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8379-8123","authenticated-orcid":true,"given":"Blaize","family":"D\u2019Angio","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-0420","authenticated-orcid":true,"given":"Aaron","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Rahim","sequence":"additional","affiliation":[{"name":"Enable Medicine, Menlo Park, CA 94025, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2845-0279","authenticated-orcid":true,"given":"Ayano","family":"Kondo","sequence":"additional","affiliation":[{"name":"Enable Medicine, Menlo Park, CA 94025, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Klufas","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-9706","authenticated-orcid":true,"given":"A. 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