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Although the immunopathogenesis of AIP and IgG4-RD is poorly understood, we previously reported that intestinal dysbiosis mediates experimental AIP through the activation of IFN-\u03b1- and IL-33-producing plasmacytoid dendritic cells (pDCs). Because intestinal dysbiosis is linked to intestinal barrier dysfunction, we explored whether the latter affects the development of AIP and autoimmune sialadenitis in MRL\/MpJ mice treated with repeated injections of polyinosinic\u2013polycytidylic acid [poly (I:C)]. Epithelial barrier disruption was induced by the administration of dextran sodium sulfate (DSS) in the drinking water. Mice co-treated with poly (I:C) and DSS, but not those treated with either agent alone, developed severe AIP, but not autoimmune sialadenitis, which was accompanied by the increased accumulation of IFN-\u03b1- and IL-33-producing pDCs. Sequencing of 16S ribosomal RNA revealed that Staphylococcus sciuri translocation from the gut to the pancreas was preferentially observed in mice with severe AIP co-treated with DSS and poly (I:C). The degree of experimental AIP, but not of autoimmune sialadenitis, was greater in germ-free mice mono-colonized with S. sciuri and treated with poly (I:C) than in germ-free mice treated with poly (I:C) alone, which was accompanied by the increased accumulation of IFN-\u03b1- and IL-33-producing pDCs. Taken together, these data suggest that intestinal barrier dysfunction exacerbates AIP through the activation of pDCs and translocation of S. sciuri into the pancreas.<\/jats:p>","DOI":"10.1093\/intimm\/dxac039","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:08:46Z","timestamp":1661990926000},"page":"621-634","source":"Crossref","is-referenced-by-count":23,"title":["Disruption of the intestinal barrier exacerbates experimental autoimmune pancreatitis by promoting the translocation of<i>Staphylococcus sciuri<\/i>into the pancreas"],"prefix":"10.1093","volume":"34","author":[{"given":"Tomoe","family":"Yoshikawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Minaga","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikue","family":"Sekai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kurimoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Masuta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah-Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiki","family":"Takamura","sequence":"additional","affiliation":[{"name":"Department of Immunology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-8064","authenticated-orcid":false,"given":"Tomohiro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"2023020910012035200_CIT0001","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMra1104650","article-title":"IgG4-related disease","volume":"366","author":"Stone","year":"2012","journal-title":"N. 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