{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:06:13Z","timestamp":1791237973836,"version":"4.1.0"},"reference-count":56,"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\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The limited translational potential of experimental animal models for human skin disease pathophysiology demands the development of more suitable immunocompetent human experimental models. Psoriasis ranks among the most prevalent human inflammatory skin disorders, initiated and manifested by the interplay of T cells with epidermal keratinocytes. Current\n                    <jats:italic>in vitro<\/jats:italic>\n                    models recapitulate psoriasis-like pathology by incorporating CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets into skin equivalents, but lack CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, key mediators of epidermal inflammation and chronic disease. Our aim was to establish a human experimental model incorporating different CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets into a human full-thickness skin equivalent (hFTSE) to investigate their individual and combined contribution to the pathogenesis of psoriasis. Across all conditions, migration of inserted T cells towards the epidermis and the secretion of psoriasis-associated cytokines (IFN-\u03b3, IL-17, TNF-\u03b1, IL-1\u03b2, CCL20, IL-6, and IL-10) was observed. Immunohistological analysis revealed psoriasis-associated alteration of epidermal differentiation, as well as enhanced expression of keratinocyte-mediated antimicrobial peptides (AMPs) in T cell-incorporated hFTSEs. Notably, the presence of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells altered the efficacy of treatment with the psoriasis drug apremilast. Overall, our findings contribute to the refinement of human skin models for studying disease pathophysiology and evaluating therapeutic responses, enabling more accurate predictions of drug efficacy and safety.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1790531","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:06:26Z","timestamp":1775801186000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["CD4+ and CD8+ T cells contribute to psoriasis phenotype when integrated into human skin equivalents for drug testing"],"prefix":"10.3389","volume":"17","author":[{"given":"Irit","family":"Vahav","sequence":"first","affiliation":[{"name":"Berlin Institute of Health (BIH) at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Immunomics - Regenerative Immunology and Aging","place":["Berlin, Germany"]},{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Movement Sciences, Tissue Function & Regeneration, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Thon","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper J.","family":"Koning","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Movement Sciences, Tissue Function & Regeneration, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC Location Vrije Universiteit Amsterdam","place":["Amsterdam, Netherlands"]},{"name":"Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit","place":["Amsterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Thiel","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health (BIH) at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Immunomics - Regenerative Immunology and Aging","place":["Berlin, Germany"]},{"name":"Si-M\/\u201dDer Simulierte Mensch\u201d, a science framework of Technische Universit\u00e4t Berlin and Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]},{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Medical Immunology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Loyal","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health (BIH) at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Immunomics - Regenerative 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