{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:23:32Z","timestamp":1791501812512,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T00:00:00Z","timestamp":1601164800000},"content-version":"vor","delay-in-days":270,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["WK9110000052"],"award-info":[{"award-number":["WK9110000052"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["1908085QH324"],"award-info":[{"award-number":["1908085QH324"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901615"],"award-info":[{"award-number":["81901615"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373187"],"award-info":[{"award-number":["81373187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871271"],"award-info":[{"award-number":["81871271"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    . This study is aimed at exploring the role of B7\u2010H4 in the pathogenesis of primary Sj\u00f6gren\u2019s syndrome (pSS) in NOD\/Ltj mouse.\n                    <jats:italic>Methods<\/jats:italic>\n                    . B7\u2010H4 expression in salivary glands was examined by IHC, and lymphocyte infiltration was showed by H&amp;E. Next, anti\u2010B7\u2010H4 mAb or immunoglobulin isotype was injected into NOD\/Ltj mice. Cytokine levels were measured by quantitative RT\u2010PCR, and immunoglobulins were measured by ELISA. T cell subsets were analyzed by flow cytometry. Last, we treated NOD\/Ltj mice with B7\u2010H4Ig and control Ig. CD4+Foxp3+ T cells were assessed by immunohistochemistry. Two\u2010tailed Student\u2019s\n                    <jats:italic>t<\/jats:italic>\n                    \u2010tests were used to detect the statistical difference in various measures between the two groups.\n                    <jats:italic>Results<\/jats:italic>\n                    . B7\u2010H4 expression was remarkably reduced in salivary glands of NOD\/Ltj mice at 15 weeks compared with the NOD\/Ltj mice at 8 weeks. Anti\u2010B7\u2010H4 mAb treatment increased lymphocyte infiltration in salivary glands. Inflammatory cytokines including IL\u201012, IL\u201018, IL\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , IFN\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , and BAFF were upregulated markedly in anti\u2010B7\u2010H4 mAb\u2010treated mice compared to IgG isotype\u2010treated mice. Flow cytometry analysis showed that anti\u2010B7\u2010H4 mAb\u2010treated mice had lower levels of CD4+Foxp3+\/CD4+ T cells in spleen. Moreover, Foxp3 mRNA levels of salivary glands were diminished in anti\u2010B7\u2010H4 mAb\u2010treated mice. Flow cytometry analysis showed that anti\u2010B7\u2010H4 mAb inhibited CD4+Foxp3+\/CD4+ T cell production, while B7\u2010H4Ig would promote na\u00efve CD4+ T into Treg differentiation. Administration with B7\u2010H4Ig displayed significantly decreased lymphocyte infiltration in salivary glands and low levels of total IgM and IgG in serum. Analysis of inflammatory cytokines in salivary glands after B7\u2010H4Ig treatment revealed that the mRNA levels of IL\u201012, IL\u20106, IL\u201018, IL\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , and IFN\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    were significantly downregulated in B7\u2010H4Ig\u2010treated mice compared to control Ig treatment. B7\u2010H4Ig\u2010treated mice had significantly higher levels of CD4+Foxp3+\/CD4+ T cells in spleen. IHC in salivary gland revealed that CD4+Foxp3+ T cells of B7\u2010H4Ig treatment mouse were more than control Ig treatment.\n                    <jats:italic>Conclusions<\/jats:italic>\n                    . Our findings implicate that B7\u2010H4 has a protective role for salivary gland epithelial cells (SGECs) and therapeutic potential in the treatment of pSS.\n                  <\/jats:p>","DOI":"10.1155\/2020\/4896727","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T19:30:59Z","timestamp":1601235059000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["B7\u2010H4 Inhibits the Development of Primary Sj\u00f6gren\u2019s Syndrome by Regulating Treg Differentiation in NOD\/Ltj Mice"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-4955","authenticated-orcid":false,"given":"Xu","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qikai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangpei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-7774","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-2596","authenticated-orcid":false,"given":"Xiaomei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,27]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573397112666160714164149"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1804598"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep141"},{"key":"e_1_2_10_4_2","first-page":"17","article-title":"Immunopathology of Sj\u00f6gren\u2019s syndrome","volume":"149","author":"Tapinos N. 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