{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T21:33:20Z","timestamp":1777757600180,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    The autoimmune hair loss disorder alopecia areata (AA), is characterized by immune privilege (IP) collapse of the hair follicle (HF) bulb resulting from a Th1-dependent inflammatory response. Although CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are recognized key drivers of the disease, it remains to be clarified whether the activation of HF resident T cells suffice to initiate IP loss and thus elicit the cascade of events leading to AA. Here, we utilized the human microdissected HF organ culture model to answer this question by activating intra- and peri-follicular HF resident T cells with \u03b1CD3\/\u03b1CD28 antibodies. TCR stimulation indeed resulted in enhanced resident T cell proliferation, as indicated by significantly increased CD3\n                    <jats:sup>+<\/jats:sup>\n                    Ki-67\n                    <jats:sup>+<\/jats:sup>\n                    cells, and higher intrafollicular CD3\n                    <jats:sup>+<\/jats:sup>\n                    T cell numbers. Furthermore, \u03b1CD3\/\u03b1CD28 stimulation promoted key signs of HF IP collapse, by increasing bulbar MHC class I and II expression and elevating MHC class II\n                    <jats:sup>+<\/jats:sup>\n                    cells numbers. We next sought to investigate whether T cell proliferation plays a central role in the TCR activation\u2013dependent collapse of the bulb IP. To test this, we co-administered the DHODH inhibitor farudodstat 1 day prior and during the stimulation with \u03b1CD3\/\u03b1CD28 in HF organ culture. Short-term treatment with farudodstat reduced the increase in T cell proliferation and significantly decreased the upregulated MHC class I and II expression induced by TCR stimulation with \u03b1CD3\/\u03b1CD28. Our results show that stimulation of HF resident T cells via TCR engagement induces an AA\u2013like phenotype in healthy human HFs\n                    <jats:italic>ex vivo<\/jats:italic>\n                    , characterized by T cell proliferation and subsequent IP collapse. DHODH inhibition with farudodstat only partially reduces T cell numbers but prevented HF IP collapse induction.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1810644","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:49:18Z","timestamp":1777466958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Resident T cell activation leads to human hair follicle immune privilege loss ex vivo, which is prevented by the DHODH inhibitor farudodstat: relevance for alopecia areata"],"prefix":"10.3389","volume":"13","author":[{"given":"Ilaria","family":"Piccini","sequence":"first","affiliation":[{"name":"QIMA Life Sciences, QIMA Monasterium GmbH","place":["M\u00fcnster, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Rouill\u00e9","sequence":"additional","affiliation":[{"name":"QIMA Life Sciences, QIMA Monasterium GmbH","place":["M\u00fcnster, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Funk","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Reconstructive Surgery Dr. Dr. med. Funk","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Mediteknia Clinic","place":["Las Palmas de Gran Canaria, Spain"]},{"name":"Ciencias de La Salud, University Fernando Pessoa Canarias","place":["Las Palmas de Gran Canaria, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Kaoukhov","sequence":"additional","affiliation":[{"name":"ASLAN Pharmaceuticals","place":["San Mateo, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Firth","sequence":"additional","affiliation":[{"name":"ASLAN Pharmaceuticals","place":["San Mateo, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amos","family":"Gilhar","sequence":"additional","affiliation":[{"name":"Technion\u2013Israel Institute of Technology","place":["Haifa, Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janin","family":"Edelkamp","sequence":"additional","affiliation":[{"name":"QIMA Life Sciences, QIMA Monasterium GmbH","place":["M\u00fcnster, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferda","family":"Cevikbas","sequence":"additional","affiliation":[{"name":"ASLAN Pharmaceuticals","place":["San Mateo, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Bertolini","sequence":"additional","affiliation":[{"name":"QIMA Life Sciences, QIMA Monasterium GmbH","place":["M\u00fcnster, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1111\/exd.14155","article-title":"Hair follicle immune privilege and its collapse in alopecia areata.","volume":"29","author":"Bertolini","year":"2020","journal-title":"Exp Dermatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1243556","DOI":"10.3389\/fimmu.2023.1243556","article-title":"Inhibition of T-cell activity in alopecia areata: recent developments and new directions.","volume":"14","author":"Passeron","year":"2023","journal-title":"Front Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1056\/NEJMra1103442","article-title":"Alopecia areata.","volume":"366","author":"Gilhar","year":"2012","journal-title":"N Engl J Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/978-1-0716-0648-3_9","article-title":"Methods to study human hair follicle growth ex vivo: human microdissected hair follicle and human full thickness skin organ culture.","volume":"2154","author":"Edelkamp","year":"2020","journal-title":"Methods Mol Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"S55","DOI":"10.1016\/0923-1811(94)90036-1","article-title":"Human hair growth in vitro: a model for the study of hair follicle biology.","volume":"7","author":"Philpott","year":"1994","journal-title":"J Dermatol Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e20231242","DOI":"10.1084\/jem.20231242","article-title":"TCR ligand potency differentially impacts PD-1 inhibitory effects on diverse signaling pathways.","volume":"220","author":"Chan","year":"2023","journal-title":"J Exp Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e18","DOI":"10.5808\/gi.23009","article-title":"Single-cell RNA sequencing identifies distinct transcriptomic signatures between PMA\/ionomycin- and \u03b1CD3\/\u03b1CD28-activated primary human T cells.","volume":"21","author":"Lee","year":"2023","journal-title":"Genomics Inform."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/nm.3645","article-title":"Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.","volume":"20","author":"Xing","year":"2014","journal-title":"Nat Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.autrev.2016.03.008","article-title":"Alopecia areata: animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies.","volume":"15","author":"Gilhar","year":"2016","journal-title":"Autoimmun. 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