Autoimmune liver diseases (AILDs), including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and IgG4-related sclerosing cholangitis, are characterised by immune dysregulation that adversely affects the hepatocytes or bile ducts. Regulatory T cells (Tregs), which are pivotal for immune tolerance, display altered function and abundance across these disorders, with notable differences between peripheral and hepatic environments. This review synthesises current evidence on disease-specific Treg alterations across AILDs, integrating findings from human studies and preclinical models. We highlight heterogeneity in Treg abundance, phenotype and function across disease subtypes, stages and tissue compartments, while examining the influence of the local immune microenvironment and gut-liver axis on Treg stability and function. We further evaluate current and emerging Treg-targeted therapeutic strategies, ranging from restoration of Treg abundance and function to disease-specific modulation of Treg responses, together with the major challenges to their clinical translation. By integrating these findings, we provide a disease-dependent and context-dependent framework for understanding Treg dysregulation in AILDs and identify key priorities for future mechanistic and translational research.

Circadian rhythms orchestrate daily oscillations in physiology and behaviour, enabling optimal alignment between internal biological processes and environmental cycles. A hierarchical system centred in the suprachiasmatic nucleus and supported by peripheral clocks across tissues ensures temporal alignment of metabolic, immune and GI functions. Within the GI tract, local clocks drive rhythmic programmes that regulate digestion, absorption, motility, hormone secretion, immune responses and interactions with the gut microbiota. Feeding-fasting cycles and microbial metabolites act as powerful zeitgebers for intestinal clocks, shaping rhythmic gene expression and intestinal metabolic oscillations. Chronodisruption-arising from misaligned light exposure, sleep disturbances or mistimed eating schedules-uncouples central and peripheral clocks. These disturbances, increasingly prevalent in shift workers, disrupt microbial rhythmicity and intestinal homeostasis. Chronodisruption contributes to metabolic disorders, including obesity, dyslipidaemia and type 2 diabetes, and increases the susceptibility to GI disorders such as IBD, IBS, GORD and colorectal cancer. Emerging therapeutic strategies aim to restore circadian alignment. Time-restricted feeding reinforces endogenous rhythmicity, improves metabolic health and restores GI rhythmic processes through entrainment of clock genes, nutrient-sensing pathways and microbial oscillations. Chronobiotics, including melatonin and phytochemicals, further offer non-invasive approaches to resynchronise disrupted clocks. Finally, chronotherapy and chronotype-tailored interventions further underscore the potential of personalised medicine based on circadian biology. Advances in research on rhythmic metabolites and interorgan metabolic coupling offer promising opportunities for understanding systemic circadian coordination. Overall, reinforcing circadian alignment holds potential for preventing and treating metabolic and GI diseases associated with modern lifestyle-induced chronodisruption.