Open AccessMechanism of indoleamine 2, 3‐dioxygenase inhibiting cardiac allograft rejection in mice
Author(s) -
Li Chuan,
Sun Zhaonan,
Yuan Fang,
Zhao Zhicheng,
Zhang Jiehong,
Zhang Baotong,
Li Hongyue,
Liu Tong,
Dai Xiangchen
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15024
Subject(s) - indoleamine 2,3 dioxygenase , immune system , immune tolerance , transplantation , catabolism , metabolite , immunosuppression , tryptophan , biology , immunology , mechanism (biology) , mixed lymphocyte reaction , heart transplantation , tryptophan metabolism , kynurenine , metabolism , medicine , t cell , endocrinology , biochemistry , philosophy , amino acid , epistemology
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.