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The specific contribution of these cytokines to the onset and severity of dacryoadenitis in the CD25-<\/jats:sup>\/-<\/jats:sup> mice has not been evaluated.<\/jats:p>\n <\/jats:sec>\n Methods<\/jats:title>\n CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17A\u2212<\/jats:sup>\/\u2212<\/jats:sup>, CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17\u2212<\/jats:sup>\/\u2212<\/jats:sup>IFN-\u03b3\u2212<\/jats:sup>\/\u2212<\/jats:sup> and CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IFN-\u03b3\u2212<\/jats:sup>\/\u2212<\/jats:sup> were used at 4, 8, 12, 16 weeks (W). Total lymphocytic infiltration was evaluated by histology and characterized by flow cytometry. Epidermal growth factor (EGF) concentration was measured in tears. Immunofluorescent staining evaluated expression of IFN-\u03b3 receptor (IFN-\u03b3R) and apoptosis. Real-time PCR evaluated inflammatory and T cell-related cytokines expression in LG. Caspase-3, -8, -9 activities was assayed in LG lysates. T helper cytokines were measured in serum by Luminex assay.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n The greatest total LG infiltration at 8 W was seen in CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17A\u2212<\/jats:sup>\/\u2212<\/jats:sup> (95%), followed by CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup> (71%) and IL-17\u2212<\/jats:sup>\/\u2212<\/jats:sup> (12%). Tear EGF concentration was in normal range in CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup> at 4 W and in very low levels in both CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup> and CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17A\u2212<\/jats:sup>\/\u2212<\/jats:sup>. CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup> had high levels of inflammatory cytokines transcripts in LG compared to IL-17\u2212<\/jats:sup>\/\u2212<\/jats:sup> mice; however, CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17A\u2212<\/jats:sup>\/\u2212<\/jats:sup> had even higher IL-1\u03b2, IFN-\u03b3R, caspase-3, -8, -9 mRNA levels, greater immunoreactivity to IFN-\u03b3R in LG acini, greater number of apoptotic+<\/jats:sup> cells and greater caspases activities in the LG at 8 W. CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17A\u2212<\/jats:sup>\/\u2212<\/jats:sup> had lower IL-13 concentration and lower IL-13\/IFN-\u03b3 ratio compared to CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup> in serum. CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IFN-\u03b3\u2212<\/jats:sup>\/\u2212<\/jats:sup> had lower number of apoptotic+<\/jats:sup> cells and decreased caspase-3 expression in LG. CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17\u2212<\/jats:sup>\/\u2212<\/jats:sup>IFN-\u03b3\u2212<\/jats:sup>\/\u2212<\/jats:sup> had lower total lymphocytic cell infiltration at 8 W (48%), CD4+<\/jats:sup>T cell infiltration and expression of IFN-\u03b3R and apoptotic+<\/jats:sup> cells in the LG and increased tear EGF concentration in tears.<\/jats:p>\n <\/jats:sec>\n Conclusions<\/jats:title>\n IFN-\u03b3 is critical for LG destruction and secretory dysfunction in the CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup> model of SS. Altered balance between IFN-\u03b3 and IL-13 in the CD25\u2212<\/jats:sup>\/\u2212<\/jats:sup>IL-17A\u2212<\/jats:sup>\/\u2212<\/jats:sup> mice accelerates LG destruction by increasing glandular apoptosis and facilitating apoptosis through increased expression of IFN-\u03b3R by glandular epithelium and activation of caspases. Targeting both IFN-\u03b3 and IL-17 may be beneficial for treating the LG inflammation in SS.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s13075-015-0582-9","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T18:41:06Z","timestamp":1425926466000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Altered balance of interleukin-13\/interferon-gamma contributes to lacrimal gland destruction and secretory dysfunction in CD25 knockout model of Sj\u00f6gren\u2019s syndrome"],"prefix":"10.1186","volume":"17","author":[{"given":"Fang","family":"Bian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia L","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M","family":"Corrales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia SA","family":"Pelegrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene A","family":"Volpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C","family":"Pflugfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia S","family":"de Paiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"582_CR1","first-page":"2609","volume":"43","author":"ME Stern","year":"2002","unstructured":"Stern ME, Gao J, Schwalb TA, Ngo M, Tieu DD, Chan CC, et al. 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