CCL20-CCR6轴介导黏膜相关恒定T细胞-M2巨噬细胞串扰驱动肝硬化免疫失调
CCL20-CCR6 axis mediates mucosal-associated invariant T-M2 macrophage crosstalk to drive immune dysregulation in liver cirrhosis.
摘要(中文译文)
肝硬化是慢性肝病的终末期，以进行性肝纤维化和持续性免疫失调为特征，然而免疫细胞间交互作用驱动疾病进展的机制仍知之甚少。在本研究中，我们整合了批量与单细胞转录组分析，并结合免疫荧光验证，探讨CCL20-CCR6轴在肝硬化进展过程中MAIT细胞与巨噬细胞相互作用中的作用。我们鉴定出八个肝硬化相关核心免疫基因（），其中CCL20选择性富集于黏膜相关恒定T细胞（MAIT），并与其活化和耗竭相关转录谱密切相关。细胞间通讯分析揭示，CCL20-CCR6轴可能特异性介导MAIT细胞与M2巨噬细胞之间的双向相互作用，在肝硬化微环境中形成疾病特异性的正反馈环路。免疫荧光染色进一步证实了CCL20、MAIT细胞和M2巨噬细胞在肝硬化组织中的富集与共定位。综上所述，这些发现支持CCL20-CCR6轴是肝硬化肝脏免疫失调和纤维化进展的关键调控因子，凸显其作为疾病活动度生物标志物及肝硬化干预治疗靶点的潜力。
Abstract
Cirrhosis is the end-stage of chronic liver disease characterized by progressive hepatic fibrosis and persistent immune dysregulation, yet the mechanisms by which immune cell crosstalk drives disease progression remain poorly understood. In the present study, we integrated bulk and single-cell transcriptomic analyses with immunofluorescence validation to investigate the role of the CCL20-CCR6 axis in MAIT cells-macrophages interactions during cirrhosis progression. We identified eight core cirrhosis-associated immune genes (), among which CCL20 was selectively enriched in mucosal-associated invariant T cells (MAIT) and closely associated with their activation- and exhaustion-related transcriptional profiles. Cell-cell communication analysis revealed that the CCL20-CCR6 axis may specifically mediate bidirectional interactions between MAIT cells and M2 macrophages, forming a disease-specific positive feedback loop within the cirrhotic microenvironment. Immunofluorescence staining further confirmed the enrichment and colocalization of CCL20, MAIT cells, and M2 macrophages in cirrhotic tissues. Collectively, these findings support the CCL20-CCR6 axis as a key regulator of hepatic immune dysregulation and fibrotic progression in liver cirrhosis, highlighting its potential as both a biomarker of disease activity and a therapeutic target for cirrhosis intervention.
如何引用
AMA
Bochen Chen, Ruoling Li, Shuya Zhang, Yiting Lou, Shuo Zhang, Jiaheng Lou, et al. CCL20-CCR6 axis mediates mucosal-associated invariant T-M2 macrophage crosstalk to drive immune dysregulation in liver cirrhosis.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1859932.
APA
Bochen Chen, Ruoling Li, Shuya Zhang, Yiting Lou, Shuo Zhang, Jiaheng Lou, et al (2026). CCL20-CCR6 axis mediates mucosal-associated invariant T-M2 macrophage crosstalk to drive immune dysregulation in liver cirrhosis.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1859932
GB/T 7714
Bochen Chen, Ruoling Li, Shuya Zhang, Yiting Lou, Shuo Zhang, Jiaheng Lou, et al. CCL20-CCR6 axis mediates mucosal-associated invariant T-M2 macrophage crosstalk to drive immune dysregulation in liver cirrhosis.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1859932.
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