Tryptophan metabolism in liver transplantation immune tolerance.

Liver transplantation is a life-saving treatment for end-stage liver disease, but long-term outcomes are limited by complications of lifelong immunosuppression. Inducing immune tolerance has become a major research priority. Tryptophan (Trp) metabolism, particularly the kynurenine pathway, is a key endogenous regulator of peripheral tolerance. This review moves beyond a simple description of metabolic routes and provides a critical, integrated analysis. We systematically compare the non-redundant immunosuppressive roles of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO2) in liver transplant immunity, dissect the Trp/kynurenine/AhR pathways that reprograms immune cell function, and incorporate gut-microbiota-dependent indole metabolism as an upstream gut-liver axis node. Clinical evidence is stratified by level, and major translational barriers, including safety risks, delivery challenges, and lack of validated biomarkers are discussed. Current data suggest that combined metabolite panels may outperform single markers, but therapeutic targeting of Trp metabolism remains a preclinical research direction rather than an established therapy.