{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:29:00Z","timestamp":1792985340492,"version":"4.5.0"},"reference-count":78,"publisher":"American Society of Hematology","issue":"2","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cutaneous T-cell lymphoma (CTCL) is a devastating lymphoid malignancy characterized by the accumulation of malignant T cells in the dermis and epidermis. Skin lesions cause serious symptoms that hamper quality of life and are entry sites for bacterial infection, a major cause of morbidity and mortality in advanced diseases. The mechanism driving the pathological processes that compromise the skin barrier remains unknown. Here, we report increased transepidermal water loss and compromised expression of the skin barrier proteins filaggrin and filaggrin-2 in areas adjacent to TOX-positive T cells in CTCL skin lesions. Malignant T cells secrete mediators (including cytokines such as interleukin 13 [IL-13], IL-22, and oncostatin M) that activate STAT3 signaling and downregulate filaggrin and filaggrin-2 expression in human keratinocytes and reconstructed human epithelium. Consequently, the repression of filaggrins can be counteracted by a cocktail of antibodies targeting these cytokines\/receptors, small interfering RNA\u2013mediated knockdown of JAK1\/STAT3, and JAK1 inhibitors. Notably, we show that treatment with a clinically approved JAK inhibitor, tofacitinib, increases filaggrin expression in lesional skin from patients with mycosis fungoides. Taken together, these findings indicate that malignant T cells secrete cytokines that induce skin barrier defects via a JAK1\/STAT3-dependent mechanism. As clinical grade JAK inhibitors largely abrogate the negative effect of malignant T cells on skin barrier proteins, our findings suggest that such inhibitors provide novel treatment options for patients with CTCL with advanced disease and a compromised skin barrier.<\/jats:p>","DOI":"10.1182\/blood.2022016690","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T16:59:08Z","timestamp":1663606748000},"page":"180-193","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":60,"title":["Malignant T cells induce skin barrier defects through cytokine-mediated JAK\/STAT signaling in cutaneous T-cell lymphoma"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8877-3486","authenticated-orcid":false,"given":"Maria","family":"Gluud","sequence":"first","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3712-0781","authenticated-orcid":false,"given":"Emil M. H.","family":"Pallesen","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7180-6384","authenticated-orcid":false,"given":"Terkild B.","family":"Buus","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-3209","authenticated-orcid":false,"given":"Lise Mette Rahbek","family":"Gjerdrum","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Zealand University Hospital, Roskilde, Denmark"},{"name":"3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise M.","family":"Lindahl","sequence":"additional","affiliation":[{"name":"4Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2173-4516","authenticated-orcid":false,"given":"Maria R.","family":"Kamstrup","sequence":"additional","affiliation":[{"name":"5Department of Dermatology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bzorek","sequence":"additional","affiliation":[{"name":"2Department of Pathology, Zealand University Hospital, Roskilde, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Danielsen","sequence":"additional","affiliation":[{"name":"4Department of Dermatology, Aarhus University Hospital, Aarhus, 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Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9687-7269","authenticated-orcid":false,"given":"Andreas","family":"Willerslev-Olsen","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6732-948X","authenticated-orcid":false,"given":"Anders","family":"Lykkebo-Vall\u00f8e","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chella Krishna","family":"Vadivel","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorbj\u00f8rn","family":"Krejsgaard","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte Menne","family":"Bonefeld","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8472-0771","authenticated-orcid":false,"given":"Carsten","family":"Geisler","sequence":"additional","affiliation":[{"name":"1LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, 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