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However, the key mechanisms that lead to immune dysregulation are not fully understood. In other types of inflammatory arthritis, T regulatory cell (Treg) dysfunction and plasticity at sites of inflammation were suggested to negatively affect peripheral tolerance. We here addressed if Treg variances associate with psoriatic disease. We collected clinical data, sera and peripheral blood mononuclear cells from 13 healthy controls, 21 psoriasis and 21 PsA patients. In addition, we obtained synovial fluid mononuclear cells from 6 PsA patients. We studied characteristics of CD4\u2009+\u2009CD25\u2009+\u2009CD127<jats:sup>lo<\/jats:sup>Foxp3\u2009+\u2009Tregs by flow cytometry and used ELISA to quantify antibodies against ADAMTSL5, a recently discovered autoantigen in psoriatic disease. In comparison with their circulating counterparts, Tregs from inflamed joints express increased levels of ICOS, CTLA-4 and TIGIT. Furthermore, synovial fluid-derived Tregs have a distinct phenotype, characterized by IL-17A production and upregulation of CD161 and ROR\u03b3t. We identified a subset of Tregs with intermediate Foxp3 expression as the major cytokine producer. Furthermore, ICOS\u2009+\u2009Tregs associate with PsA disease activity as measured by PASDAS. Lastly, we observed that presence of the Foxp3<jats:sup>int<\/jats:sup> Tregs associates with an increased abundance of anti-ADAMTSL5 autoantibodies. Tregs derived from the inflammatory environment of inflamed PsA joints exhibit a distinct phenotype, which associates with loss of peripheral immune tolerance in psoriatic disease.<\/jats:p>","DOI":"10.1038\/s41598-022-24924-w","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T16:16:49Z","timestamp":1669825009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Regulatory T cells in psoriatic arthritis: an IL-17A-producing, Foxp3intCD161\u2009+\u2009ROR\u03b3t\u2009+\u2009ICOS\u2009+\u2009phenotype, that associates with the presence of ADAMTSL5 autoantibodies"],"prefix":"10.1038","volume":"12","author":[{"given":"Juli\u00ebtte N.","family":"Pouw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel A. 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