Diverse Subsets of γδT Cells and Their Specific Functions Across Liver Diseases.

Abstract

γδT cells, a distinct group of T lymphocytes, serve as a link between innate and adaptive immune responses. They are pivotal in the pathogenesis of various liver disorders, such as viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), liver fibrosis, autoimmune liver diseases, and hepatocellular carcinoma (HCC). Despite their importance, the functional diversity and regulatory mechanisms of γδT cells remain incompletely understood. Recent advances in high-throughput single-cell sequencing and spatial transcriptomics have revealed significant heterogeneity among γδT cell subsets, particularly Vδ1⁺ and Vδ2⁺, which exhibit distinct immunological roles. Vδ1⁺ T cells are mainly tissue-resident and contribute to tumor immunity and chronic inflammation, while Vδ2⁺ T cells, predominantly found in peripheral blood, play roles in systemic immune surveillance but may undergo dysfunction in chronic liver diseases. Additionally, γδT17 cells exacerbate inflammation in NAFLD and ALD, whereas IFN-γ-secreting γδT cells contribute to antiviral and antifibrotic responses. These discoveries have laid the foundation for the creation of innovative solutions. γδT cell-based immunotherapeutic approaches, such as adoptive cell transfer, immune checkpoint inhibition, and strategies targeting metabolic pathways. Future research should focus on harnessing γδT cells' therapeutic potential through targeted interventions, offering promising prospects for precision immunotherapy in liver diseases.