{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:06:33Z","timestamp":1784819193577,"version":"3.55.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022606","name":"Almirall","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n T cell autoreactivity against the autoantigens LL37 and ADAMTSL5 contributes to inflammation in a subset of psoriatic patients. The immunological mechanisms underlying the treatment response in patients showing autoreactivity remain incompletely understood in clinical settings. This study investigated the impact of tildrakizumab on circulating immune populations and on autoantigen-specific T cell reactivity.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Patients with moderate-to-severe psoriasis were enrolled and treated with tildrakizumab according to clinical practice. T cells autoreactivity to LL37 and ADAMTSL5 was assessed at baseline using a stimulation index (SI&gt;2). Longitudinal changes in circulating T cell subsets were analyzed using multiparametric flow cytometry.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Twenty of 38 psoriatic patients (52.6%) displayed circulating autoreactive T cells (SI&gt;2) to LL37 and\/or ADAMTSL5, compared with 5 of 33 healthy donors (15.2%). Baseline frequencies of Ki67\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n , and IL-17\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n \/CD8\n +<\/jats:sup>\n T cell populations positively correlated with PASI. Stimulation of PBMCs with LL37 or ADAMTSL5 induced Th17- and Th1-related cytokines, but not Th2-related cytokines. During treatment, tildrakizumab significantly modulated multiple circulating T cell subsets, including Ki67\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n , Ki67\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n , Ki67\n +<\/jats:sup>\n Th17, Th17, and Ki67\n +<\/jats:sup>\n Tregs, and markedly reduced autoreactivity to both autoantigens. Notably, clinical improvement strongly correlated with reductions in Ki67\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n and Ki67\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n T cell frequencies. LL37-reactive patients exhibited a poorer clinical response at weeks 40 and 52.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In autoreactive patients, tildrakizumab effectively modulated circulating T cell proliferation and reduced autoantigen-specific responses over time. LL37-reactive patients showed distinct long-term responses, suggesting that autoantigen-reactive subjects may represent a more treatment-challenging subgroup within the psoriatic population.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1795117","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:01:02Z","timestamp":1775800862000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of tildrakizumab on circulating T cells in autoreactive psoriatic patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Paola","family":"Facheris","sequence":"first","affiliation":[{"name":"Dermatology Unit, Humanitas Research Hospital - IRCCS, Rozzano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Favaro","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Humanitas Research Hospital - IRCCS, Rozzano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Valenti","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Humanitas Research Hospital - IRCCS, Rozzano","place":["Milan, Italy"]},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Humanitas Research Hospital - IRCCS, Rozzano","place":["Milan, Italy"]},{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo G.","family":"Borroni","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Humanitas Research Hospital - IRCCS, Rozzano","place":["Milan, Italy"]},{"name":"Department of Biomedical Sciences, Humanitas 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