Regulatory T cells in liver diseases: roles and therapeutic targeting

Abstract

The liver is an immune-tolerogenic organ in which coordinated interactions between resident and infiltrating immune cells maintain hepatic and systemic homeostasis. Disruption of this balance can lead to chronic inflammation, fibrogenesis, infection, and malignant transformation, highlighting the importance of immune regulation in liver disease. Regulatory T cells (Tregs) are important components of immune regulation that restrain excessive immune activation and contribute to hepatic homeostasis. However, their roles in liver diseases are highly context-dependent and shaped by disease etiology, stage, tissue localization, and the surrounding microenvironment. Tregs can protect against autoimmune and inflammatory injury, whereas their phenotypic adaptation, aberrant accumulation, or impaired function may contribute to persistent infection, metabolic and fibrotic disease progression, and tumor immune escape. In this review, we summarize the roles of Tregs across major liver diseases and their interactions with the hepatic immune microenvironment. We also discuss Treg-targeted strategies, including cytokine-mediated expansion, adoptive transfer, selective depletion, and engineered Tregs, with particular attention to chimeric antigen receptor-engineered Treg (CAR-Treg). Key challenges for clinical translation include Treg heterogeneity, tissue-specific trafficking, functional stability, target specificity, and limited concordance between preclinical findings and clinical outcomes.

The authors' abstract, as published at the source. Cell Communication and Signaling, 2026 · DOI ↗