Shanxi Provincial Children's Hospital, Taiyuan, China.
Department of Pediatrics, Shanxi Medical University, Taiyuan, China.
BMC Pediatr. 2024 Oct 17;24(1):669. doi: 10.1186/s12887-024-05152-9.
Biliary atresia (BA) has diverse and unclear pathogenesis, which may be related to immune response in response to a foreign stimulus. T follicular helper (Tfh) cells have been found to play an important role in various immune diseases.
To investigate the expression of Tfh cells in BA and non-BA cholestatic diseases in children.
Transcriptome sequencing and Gene Ontology (GO) enrichment analysis were performed to investigate the differences in gene expression between the BA group and the non-BA cholestasis group. Study the distribution of Tfh cells in liver tissues of the BA and non-BA cholestatic groups through single sample gene set enrichment analysis (ssGSEA). Tfh cells (CD3Bcl6) in liver tissues from BA patients were labeled by double immunofluorescent staining to verify their distribution in the liver.
Transcriptome sequencing showed differences in gene expression between the BA group and the non-BA cholestasis group. A total of 808 genes were up-regulated and 405 genes were down-regulated in BA, suggesting that there might be a specific immune response in BA. GO enrichment analysis showed that BA group had augmented response to foreign stimulus and increased metabolic process compared to the non-BA cholestatic group. The relative proportion of immune cells was analyzed by ssGSEA method. The proportions of Tfh cells, activated B cells, CD4 T cells, memory B cells and Th2 cells were higher in the BA group than in the non-BA cholestatic group. Fluorescence immunostaining showed that Tfh cells were significantly increased in liver tissue samples of the BA group compared to the non-BA cholestasis group, which was consistent with the transcriptome sequencing results.
Tfh cells share in immune cascade involvement in BA. Our work support immune pathogenesis of the in response to a stimulus that might be foreign in BA.
先天性胆道闭锁（BA）的发病机制多样且不明确，可能与针对外来刺激的免疫反应有关。滤泡辅助性 T 细胞（Tfh）已被发现在各种免疫性疾病中发挥重要作用。
探讨 Tfh 细胞在儿童 BA 和非 BA 胆汁淤积性疾病中的表达。
采用转录组测序和基因本体论（GO）富集分析，探讨 BA 组与非 BA 胆汁淤积组基因表达的差异。通过单样本基因集富集分析（ssGSEA）研究 BA 和非 BA 胆汁淤积组肝组织中 Tfh 细胞的分布。通过双免疫荧光染色标记 BA 患者肝组织中的 Tfh 细胞（CD3+Bcl6），验证其在肝内的分布。
转录组测序显示 BA 组与非 BA 胆汁淤积组基因表达存在差异。BA 组有 808 个基因上调，405 个基因下调，提示 BA 可能存在特定的免疫反应。GO 富集分析显示，与非 BA 胆汁淤积组相比，BA 组对外来刺激的反应增强，代谢过程增加。采用 ssGSEA 方法分析免疫细胞的相对比例。BA 组的 Tfh 细胞、活化 B 细胞、CD4 T 细胞、记忆 B 细胞和 Th2 细胞比例均高于非 BA 胆汁淤积组。荧光免疫染色显示，BA 组肝组织 Tfh 细胞明显高于非 BA 胆汁淤积组，与转录组测序结果一致。
Tfh 细胞共同参与 BA 的免疫级联反应。我们的工作支持 BA 中针对外来刺激的免疫发病机制，可能为 BA 提供新的治疗靶点。
