Yiping Xu, Jiankun Liang, Yurong Cai, Zhe Wen, Jianguo Wang
{"title":"Blockade of B-cell-activating factor may alleviate liver injury by restraining interferon-γ expression in T cells in experimental biliary atresia.","authors":"Yiping Xu, Jiankun Liang, Yurong Cai, Zhe Wen, Jianguo Wang","doi":"10.1007/s00383-025-06000-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The primary pathogenetic factor for biliary atresia is an atypical immune response. Previous studies have suggested that the expression of B cell-activating factor is upregulated in BA and BAFF is related to T-cell function. However, the way in which BAFF influences T cell function in BA is still not fully clarified. We therefore investigated the effects of BAFF on T cells in experimental biliary atresia.</p><p><strong>Methods: </strong>BAFF levels were measured in serum and liver of patients with BA and controls. Immunofluorescence analysis was performed to assess the co-localization of BAFF with myeloid cells (CD14 or CD68) in liver biopsies. A multiplex assay (MAGPIX) was used to measure the levels of Th1 [interferon (IFN)-γ], Th2 [interleukin (IL)-4], and Th17 (IL-17). IFN-γ expression was measured in CD4<sup>+</sup> and CD8<sup>+</sup> T cells in vitro. An anti-BAFF antibody was administered in a rhesus rotavirus (RRV)-induced BA model to assess the effect of BAFF. Finally, survival, histology, liver function index, liver immune cell subsets, and cytokine production were analyzed.</p><p><strong>Results: </strong>BAFF expression was significantly higher in patients with BA than controls. Furthermore, BAFF levels in liver supernatants significantly correlated with liver inflammation severity in patients with BA. In addition, BAFF levels positively correlated with IFN-γ levels. Serum BAFF combined with GGT may offer a more reliable approach for confirming the diagnosis of BA. In vitro experiments revealed that BAFF increased IFN-γ expression in CD4<sup>+</sup> and CD8<sup>+</sup> T cells of infants with BA. BAFF inhibition was associated with a decrease in portal tract inflammation and IFN-γ expression in CD4<sup>+</sup> and CD8<sup>+</sup> T cells, with the simultaneous expansion of regulatory T cells in an RRV-induced BA model.</p><p><strong>Conclusion: </strong>BAFF may participate in inflammatory responses in BA by affecting T cells, suggesting the potential role of BAFF in BA pathogenesis.</p>","PeriodicalId":19832,"journal":{"name":"Pediatric Surgery International","volume":"41 1","pages":"101"},"PeriodicalIF":1.5000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Surgery International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00383-025-06000-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The primary pathogenetic factor for biliary atresia is an atypical immune response. Previous studies have suggested that the expression of B cell-activating factor is upregulated in BA and BAFF is related to T-cell function. However, the way in which BAFF influences T cell function in BA is still not fully clarified. We therefore investigated the effects of BAFF on T cells in experimental biliary atresia.
Methods: BAFF levels were measured in serum and liver of patients with BA and controls. Immunofluorescence analysis was performed to assess the co-localization of BAFF with myeloid cells (CD14 or CD68) in liver biopsies. A multiplex assay (MAGPIX) was used to measure the levels of Th1 [interferon (IFN)-γ], Th2 [interleukin (IL)-4], and Th17 (IL-17). IFN-γ expression was measured in CD4+ and CD8+ T cells in vitro. An anti-BAFF antibody was administered in a rhesus rotavirus (RRV)-induced BA model to assess the effect of BAFF. Finally, survival, histology, liver function index, liver immune cell subsets, and cytokine production were analyzed.
Results: BAFF expression was significantly higher in patients with BA than controls. Furthermore, BAFF levels in liver supernatants significantly correlated with liver inflammation severity in patients with BA. In addition, BAFF levels positively correlated with IFN-γ levels. Serum BAFF combined with GGT may offer a more reliable approach for confirming the diagnosis of BA. In vitro experiments revealed that BAFF increased IFN-γ expression in CD4+ and CD8+ T cells of infants with BA. BAFF inhibition was associated with a decrease in portal tract inflammation and IFN-γ expression in CD4+ and CD8+ T cells, with the simultaneous expansion of regulatory T cells in an RRV-induced BA model.
Conclusion: BAFF may participate in inflammatory responses in BA by affecting T cells, suggesting the potential role of BAFF in BA pathogenesis.
期刊介绍:
Pediatric Surgery International is a journal devoted to the publication of new and important information from the entire spectrum of pediatric surgery. The major purpose of the journal is to promote postgraduate training and further education in the surgery of infants and children.
The contents will include articles in clinical and experimental surgery, as well as related fields. One section of each issue is devoted to a special topic, with invited contributions from recognized authorities. Other sections will include:
-Review articles-
Original articles-
Technical innovations-
Letters to the editor