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Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sj\u00f6gren\u2019s syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD\/ShiLtJ mice repeatedly during a 9-day period. PD-L1 blockade accelerated leukocyte infiltration and caspase-3 activation in the submandibular gland (SMG), production of antinuclear and anti-M3 muscarinic acetylcholine receptor (M3R) autoantibodies and impairment of saliva secretion, indicative of accelerated development and onset of SS. The effect of PD-L1 blockade was associated with increased T- and B cells and T helper 1 cytokine IFN-\u03b3 in the SMG. Local administration of exogenous IFN-\u03b3 to the SMG led to impaired salivary secretion accompanied by down-regulation of aquaporin 5 and an increase in anti-M3R autoantibodies. Conversely, neutralization of IFN-\u03b3 markedly improved salivary secretion and aquaporin 5 expression in anti-PD-L1-treated NOD\/ShiLtJ mice. Hence, endogenous PD-L1 hinders the development and onset of SS in NOD mice, in part by suppressing IFN-\u03b3 production.<\/jats:p>","DOI":"10.1038\/srep39105","type":"journal-article","created":{"date-parts":[[2016,12,14]],"date-time":"2016-12-14T12:20:33Z","timestamp":1481718033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Endogenous programmed death ligand-1 restrains the development and onset of Sj\u04e7gren\u2019s syndrome in non-obese diabetic mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Jing","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-O.","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihisa","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,14]]},"reference":[{"key":"BFsrep39105_CR1","doi-asserted-by":"crossref","unstructured":"Jin, J. 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