Han Huan-Qin, Bao Jia-Min, Deng Wei, Guo Wei-Fang, Li Yi-Fan, Zheng Wei-Qiang, Liu Hua-Feng
The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China.
Department of Infectious Diseases and Hepatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong Province, China.
World J Hepatol. 2025 Aug 27;17(8):109685. doi: 10.4254/wjh.v17.i8.109685.
T helper 17 (Th17) cell infiltration and interleukin (IL)-17 secretion in intrahepatic small bile ducts is a critical driver of immune-mediated injury in primary biliary cholangitis (PBC). IL-6 is an essential upstream activator of Th17 cells. Basophil-derived IL-6 promotes the differentiation of CD4+ T cells and Th1 cells into Th17 cells, thereby regulating their immunological functions.
To investigate the activation status and cytokine expression of basophils in PBC, elucidating potential mechanisms through which basophils contribute to its pathogenesis.
This single-center retrospective case-control study conducted at Guangdong Medical University Affiliated Hospital (China) between September 2019 and August 2024 enrolled 65 consecutive treatment-naïve patients with PBC (PBC group), 65 age- and sex-matched patients with chronic hepatitis B (CHB group), and 65 healthy controls (Normal group). Fourteen participants per group (subgroup) were randomly selected for flow cytometry analysis of basophil proportion, activation markers (CD203c and CD62 L mean fluorescence intensity), IL-6-positive basophils (IL-6+ basophils as a percentage of total basophils), and IL-17-positive T lymphocytes (CD3+CD4+IL-17+ cells) proportion among T cells. Data were analyzed using Kruskal-Wallis and tests as appropriate.
Routine blood tests revealed significantly higher basophil counts and proportions in the PBC group compared to the CHB and Normal groups ( < 0.001 for both comparisons), with no significant differences between the CHB and Normal groups ( = 0.201). Flow cytometry revealed a higher basophil proportion in the PBC subgroup compared to the CHB ( = 0.011) and Normal subgroups ( < 0.001). The mean fluorescence intensity of CD203c on basophil surfaces was elevated in the PBC subgroup compared to the CHB ( = 0.032) and Normal subgroups ( = 0.039). The proportion of IL-6+ basophils was significantly higher in the PBC subgroup than in the CHB ( < 0.01) and Normal subgroups ( < 0.001). Similarly, the Th17 cell proportion was markedly elevated in the PBC compared to the CHB ( < 0.001) and Normal subgroups ( < 0.001).
Patients with PBC have increased peripheral basophil counts with enhanced activation. Activated basophils have increased IL-6 expression, which may indirectly induce Th17 cell proliferation and contribute to PBC pathogenesis.
肝内小胆管中的辅助性T细胞17（Th17）细胞浸润和白细胞介素（IL）-17分泌是原发性胆汁性胆管炎（PBC）免疫介导损伤的关键驱动因素。IL-6是Th17细胞必不可少的上游激活因子。嗜碱性粒细胞衍生的IL-6促进CD4+T细胞和Th1细胞分化为Th17细胞，从而调节其免疫功能。
研究PBC中嗜碱性粒细胞的激活状态和细胞因子表达，阐明嗜碱性粒细胞参与其发病机制的潜在机制。
本单中心回顾性病例对照研究于2019年9月至2024年8月在中国广东医科大学附属医院进行，连续纳入65例未经治疗的PBC患者（PBC组）、65例年龄和性别匹配的慢性乙型肝炎患者（CHB组）和65例健康对照者（正常组）。每组（亚组）随机选取14名参与者，进行流式细胞术分析嗜碱性粒细胞比例、激活标志物（CD203c和CD62L平均荧光强度）、IL-6阳性嗜碱性粒细胞（IL-6+嗜碱性粒细胞占嗜碱性粒细胞总数的百分比）以及T细胞中IL-17阳性T淋巴细胞（CD3+CD4+IL-17+细胞）比例。数据采用Kruskal-Wallis检验和适当的检验进行分析。
常规血液检查显示，与CHB组和正常组相比，PBC组嗜碱性粒细胞计数和比例显著更高（两组比较均P<0.001），CHB组和正常组之间无显著差异（P=0.201）。流式细胞术显示，与CHB亚组（P=0.011）和正常亚组（P<0.001）相比，PBC亚组嗜碱性粒细胞比例更高。与CHB亚组（P=0.032）和正常亚组（P=0.039）相比，PBC亚组嗜碱性粒细胞表面CD203c的平均荧光强度升高。PBC亚组IL-6+嗜碱性粒细胞比例显著高于CHB亚组（P<0.01）和正常亚组（P<0.001）。同样，与CHB亚组（P<0.001）和正常亚组（P<0.001）相比，PBC组Th17细胞比例显著升高。
PBC患者外周嗜碱性粒细胞计数增加且激活增强。激活的嗜碱性粒细胞IL-6表达增加，这可能间接诱导Th17细胞增殖并参与PBC发病机制。
