Invariant natural killer T cells (iNKT cells) constitute a specialized subset of lymphocytes that bridges innate and adaptive immunity through a combination of traits characteristic of both conventional T cells and innate immune cells. iNKT cells are characterized by their invariant T cell receptors and discerning recognition of lipid antigens, which are presented by the non-classical MHC molecule, CD1d. Within the hepatic milieu, iNKT cells hold heightened prominence, contributing significantly to the orchestration of organ homeostasis. Their unique positioning to interact with diverse cellular entities, ranging from epithelial constituents like hepatocytes and cholangiocytes to immunocytes including Kupffer cells, B cells, T cells, and dendritic cells, imparts them with potent immunoregulatory abilities. Emergering knowledge of liver iNKT cells subsets enable to explore their therapeutic potential in autoimmne liver diseases. This comprehensive review navigates the landscape of iNKT cell investigations in immune-mediated cholangiopathies, with a particular focus on primary biliary cholangitis and primary sclerosing cholangitis, across murine models and human subjects to unravel the intricate involvements of iNKT cells in liver autoimmunity. Additionally, we also highlight the prospectives of iNKT cells as therapeutic targets in cholangiopathies. Modulation of the equilibrium between regulatory and proinflammatory iNKT subsets can be defining determinant in the dynamics of hepatic autoimmunity. This discernment not only enriches our foundational comprehension but also lays the groundwork for pioneering strategies to navigate the multifaceted landscape of liver autoimmunity.

中文翻译：

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自身免疫性胆管病中不变的自然杀伤 T 细胞：机制见解和治疗意义

不变的自然杀伤 T 细胞(iNKT 细胞) 构成淋巴细胞的特殊亚群，通过传统 T 细胞和先天免疫细胞特征的组合，在先天免疫和适应性免疫之间架起桥梁。iNKT 细胞的特点是具有不变的 T 细胞受体和对脂质抗原的敏锐识别，脂质抗原由非经典 MHC 分子 CD1d 呈递。在肝脏环境中，iNKT 细胞具有高度的重要性，对器官稳态的协调做出了重大贡献。它们独特的定位与多种细胞实体相互作用，从肝细胞和胆管细胞等上皮成分到库普弗细胞、B 细胞、T 细胞和树突状细胞等免疫细胞，赋予它们强大的免疫调节能力。肝脏 iNKT 细胞亚群的新知识有助于探索其在自身免疫性肝病中的治疗潜力。这篇全面的综述探讨了 iNKT 细胞在免疫介导的胆管病中的研究前景，特别关注原发性胆汁性胆管炎和原发性硬化性胆管炎，跨越小鼠模型和人类受试者，以揭示 iNKT 细胞在肝脏自身免疫中的复杂参与。此外，我们还强调了 iNKT 细胞作为胆管病治疗靶点的前景。调节调节性 iNKT 亚群和促炎性 iNKT 亚群之间的平衡可能是肝脏自身免疫动力学的决定因素。这种洞察力不仅丰富了我们的基础理解，而且为探索肝脏自身免疫多方面景观的开创性策略奠定了基础。