Blockade of B-cell-activating factor may alleviate liver injury by restraining interferon-γ expression in T cells in experimental biliary atresia.

IF 1.5 3区 医学 Q2 PEDIATRICS
Yiping Xu, Jiankun Liang, Yurong Cai, Zhe Wen, Jianguo Wang
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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.

阻断b细胞活化因子可能通过抑制实验性胆道闭锁时T细胞中干扰素γ的表达来减轻肝损伤。
背景:胆道闭锁的主要致病因素是一种非典型免疫反应。既往研究提示BA中B细胞活化因子表达上调,BAFF与t细胞功能有关。然而,BAFF在BA中影响T细胞功能的方式仍未完全阐明。因此,我们研究了BAFF在实验性胆道闭锁中对T细胞的影响。方法:测定BA患者和对照组血清和肝脏中BAFF水平。采用免疫荧光分析评估肝活检中BAFF与骨髓细胞(CD14或CD68)的共定位。采用多重测定法(MAGPIX)测定Th1[干扰素(IFN)-γ]、Th2[白细胞介素(IL)-4]和Th17 (IL-17)的水平。体外检测CD4+和CD8+ T细胞中IFN-γ的表达。在恒河轮状病毒(RRV)诱导的BA模型中注射抗BAFF抗体,以评估BAFF的作用。最后,分析存活、组织学、肝功能指数、肝免疫细胞亚群和细胞因子的产生。结果:BAFF在BA患者中的表达明显高于对照组。此外,BA患者肝脏上清液中BAFF水平与肝脏炎症严重程度显著相关。BAFF水平与IFN-γ水平呈正相关。血清BAFF联合GGT可能为确认BA的诊断提供更可靠的方法。体外实验显示,BAFF可提高BA患儿CD4+和CD8+ T细胞中IFN-γ的表达。在rrv诱导的BA模型中,BAFF抑制与门道炎症和CD4+和CD8+ T细胞中IFN-γ表达的减少有关,同时调节T细胞的扩增。结论:BAFF可能通过影响T细胞参与BA的炎症反应,提示BAFF在BA发病中的潜在作用。
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来源期刊
CiteScore
3.00
自引率
5.60%
发文量
215
审稿时长
3-6 weeks
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
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