{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:44:58Z","timestamp":1791229498032,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T00:00:00Z","timestamp":1578355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Little is known about the pathogenesis of scleromyxedema, a life\u2010threatening fibromucinosis disease with immunological dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate on T\u2010cell phenotype, function and cytokine biology in search of new insights supporting the immunopathogenesis of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed the frequency of circulating lymphocyte subsets, the T\u2010cell maturation stage, the generation of antigen\u2010specific T\u2010cell lines and T\u2010cell cytokine secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis of T\u2010cell maturation stage and the TCR spectratyping findings revealed that scleromyxedema patients showed clear immunological signs of long\u2010lasting immune system activation and stimulation leading to a skewed T\u2010cell repertoire. Moreover, these analyses showed that both CD4+ and CD8+ T cells from scleromyxedema patients have a profound deficiency (even after stimulation) relatively to the production of IFN\u2010\u03b3 and IL17 with respect to healthy donor control cells, while they are massively skewed towards IL4 secretion after stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data indicate that a chronic Th2\u2010skewed T\u2010cell response against an unknown target antigen leading to abnormally high IL4 secretion, a pro\u2010fibrotic cytokine, is a main immunological hallmark of scleromyxedema patients. These results, never reported before, may have a translational therapeutic value due to the availability of anti\u2010IL4 agents such as dupilumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdv.16136","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T06:22:26Z","timestamp":1575354146000},"page":"1092-1097","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Increased frequency of interleukin\u20104 and reduced frequency of interferon\u2010\u03b3 and IL\u201017\u2010producing CD4+ and CD8+ cells in scleromyxedema"],"prefix":"10.1111","volume":"34","author":[{"given":"F.","family":"Kalli","sequence":"first","affiliation":[{"name":"Centre of Excellence for Biomedical Research University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Cioni","sequence":"additional","affiliation":[{"name":"Section\u00a0of Dermatology DISSAL, University of Genoa Genoa Italy"},{"name":"Section\u00a0of Pathology Department of Surgical and Morphological Sciences University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Parodi","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Biomedical Research University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Altosole","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Biomedical Research University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Ferrera","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Biomedical Research University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Barra","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine Universit\u00e0 della Campania \u201cL. Vanvitelli\u201d Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"De Palma","sequence":"additional","affiliation":[{"name":"Institute of Protein Biochemistry CNR Napoli Italy"},{"name":"Department of Internal Medicine University of Genoa\u2010 IRCCS Ospedale Policlinico San Martino Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Fenoglio","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Biomedical Research University of Genoa Genoa Italy"},{"name":"Department of Internal Medicine University of Genoa\u2010 IRCCS Ospedale Policlinico San Martino Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Filaci","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Centre of Excellence for Biomedical Research University of Genoa Genoa Italy"},{"name":"Bioterapy Unit IRCCS Ospedale Policlinico San Martino Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2227-581X","authenticated-orcid":false,"given":"F.","family":"Rongioletti","sequence":"additional","affiliation":[{"name":"Section\u00a0of Pathology Department of Surgical and Morphological Sciences University of Genoa Genoa Italy"},{"name":"Department of Medical Science and Public Health Unit of Dermatology University of Cagliari Cagliari 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