Mechanism of indoleamine 2, 3-dioxygenase inhibiting cardiac allograft rejection in mice

Abstract

Indoleamine 2, 3-dioxygenase (IDO)-mediated regulation of tryptophan metabolism plays an important role in immune tolerance in transplantation, but it has not been elucidated which mechanism specifically induces the occurrence of immune tolerance. Our study revealed that IDO exerts immunosuppressive effects through two pathways in mouse heart transplantation, ‘tryptophan depletion’ and ‘tryptophan metabolite accumulation’. The synergism between IDO+DC and TC (tryptophan catabolic products) has stronger inhibitory effects on T lymphocyte proliferation and mouse heart transplant rejection than the two intervention factors alone, and significantly prolong the survival time of donor-derived transplanted skin. This work demonstrates that the combination of IDO+DC and TC can induce immune tolerance to a greater extent, and reduce the rejection of transplanted organs.