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Sj\u00f6gren\u2019s syndrome (SS) is a chronic autoimmune disease predominantly affecting women and is characterised by sicca symptoms including oral and ocular dryness. The aim of this study was to investigate an association between IL-2R and Treg function in patients with SS of different severity defined by the salivary flow rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a cross-sectional study, we determined plasma soluble IL-2R (sIL-2R) levels in women with SS (<jats:italic>n<\/jats:italic>=97) and healthy females (<jats:italic>n<\/jats:italic>=50) using ELISA. A subset of those (<jats:italic>n<\/jats:italic>=51) was screened for Treg function measured by the STAT5 signalling response to IL-2 using phospho-flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that elevated plasma levels of sIL-2R were positively associated with the severity of SS reflected by a pathologically low salivary flow. Phospho-flow analysis revealed that patients with SS have a significantly lower frequency of pSTAT5<jats:sup>+<\/jats:sup>Tregs upon IL-2 stimulation compared with healthy individuals, while the frequency of Tregs and pSTAT5 in conventional T cells remained unchanged. In addition, we observed more pSTAT5<jats:sup>+<\/jats:sup>Tregs at baseline in patients with SS, which is significantly associated with seropositivity and elevated sIL-2R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data indicates that Tregs have a weakened immunosuppressive function in patients with SS due to impaired IL-2\/IL-2R signalling capacity. This could mediate lymphocytic infiltration into salivary glands inducing sicca symptoms. We believe that sIL-2R could act as a useful indicator for SS and disease severity.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13075-022-02769-y","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T10:04:59Z","timestamp":1651917899000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Impaired activation of STAT5 upon IL-2 stimulation in Tregs and elevated sIL-2R in Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-0179","authenticated-orcid":false,"given":"Magdalena","family":"Keindl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brith","family":"Bergum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan G.","family":"Brun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hammenfors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Jonsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriya","family":"Lyssenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Appel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"issue":"1","key":"2769_CR1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.immunol.26.021607.090357","volume":"26","author":"TR Malek","year":"2008","unstructured":"Malek TR. 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