Koda Yuzo, Kasuga Ryosuke, Taniki Nobuhito, Kanai Takanori, Nakamoto Nobuhiro
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Mitsubishi Tanabe Pharma Corporation, Kanagawa, Japan.
Inflamm Regen. 2025 Jul 4;45(1):21. doi: 10.1186/s41232-025-00387-0.
The liver presents a unique immune system. Liver diseases are closely associated with the immune system. Disruption of the tightly regulated balance between immune activation and tolerance induction leads to the development and worsening of immune-related liver diseases. T cells play diverse crucial roles in the immune system, and they have long been known to induce inflammation through direct tissue damage by effector molecules and the recruitment of effector cells via chemokines. Additionally, T cells interact with B cells to induce autoantibodies, promoting tissue inflammation and dysfunction through the deposition of IgG and immune complexes in the tissues. Recent advances in omics technologies, including single-cell RNA sequencing and spatial transcriptomics, have elucidated the role of T cells in the progression and recovery of liver fibrosis. Moreover, comprehensive and unbiased information can now be obtained from small samples of human and mouse tissues, which advances our understanding of tissue-specific functions of T cells, including resident memory T cells, peripheral helper T cells, and tissue Tregs. However, significant unmet needs remain in the fields of immune-related liver diseases. In this review, we discuss the T cell biology and its role in autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and metabolic-associated steatohepatitis (MASH), which are non-viral liver diseases exhibiting a strong involvement of immunity and inflammation. Furthermore, the latest therapeutic concepts for the diseases and associated drugs targeting T cells have been overviewed.
肝脏具有独特的免疫系统。肝脏疾病与免疫系统密切相关。免疫激活和耐受诱导之间严格调控的平衡被打破会导致免疫相关性肝脏疾病的发生和恶化。T细胞在免疫系统中发挥着多种关键作用,长期以来人们已知它们可通过效应分子直接造成组织损伤以及经由趋化因子募集效应细胞来引发炎症。此外,T细胞与B细胞相互作用以诱导自身抗体,通过IgG和免疫复合物在组织中的沉积促进组织炎症和功能障碍。包括单细胞RNA测序和空间转录组学在内的组学技术的最新进展已经阐明了T细胞在肝纤维化进展和恢复中的作用。此外,现在可以从小样本的人类和小鼠组织中获得全面且无偏差的信息,这加深了我们对T细胞组织特异性功能的理解,包括驻留记忆T细胞、外周辅助性T细胞和组织调节性T细胞。然而,在免疫相关性肝脏疾病领域仍存在重大未满足的需求。在本综述中,我们讨论了T细胞生物学及其在自身免疫性肝炎(AIH)、原发性硬化性胆管炎(PSC)、原发性胆汁性胆管炎(PBC)和代谢相关脂肪性肝炎(MASH)中的作用,这些都是非病毒性肝脏疾病,显示出免疫和炎症的强烈参与。此外,还概述了这些疾病的最新治疗理念以及针对T细胞的相关药物。
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