Trp-IDO1,2/TDO2-Kyn代谢通路介导类风湿关节炎的研究进展

Progress in research of Trp-IDO1,2/TDO2-Kyn metabolic pathway in the pathogenesis of rheumatoid arthritis

类风湿关节炎(rheumatoid arthritis, RA)是以自身反应性T细胞和B细胞过度活化,自身抗体大量产生为特征,多关节受累为主要表现的自身免疫病。在遗传和环境等因素影响下,固有免疫和适应性免疫功能紊乱是其发病的根本原因。近年来,'免疫代谢学'快速发展,在不同能量代谢途径及相关分子调控免疫细胞分化与功能等方面取得重要进展。多项研究表明, Trp-IDO1,2/TDO2-Kyn代谢通路介导了RA等自身免疫病的病理机制和发生发展。本文综述了此代谢通路中色氨酸(tryptophan, Trp)和犬尿氨酸(kynurenine, Kyn)等代谢物以及限速酶吲哚胺-2,3-双加氧酶1 (indoleamine 2,3-dioxygenase 1, IDO1)、吲哚胺-2,3-双加氧酶2 (indoleamine 2, 3-dioxygenase 2, IDO2)和色氨酸-2,3-双加氧酶2 (tryptophan-2,3-dioxygenase 2, TDO2)介导RA炎症免疫反应和滑膜炎症的作用和研究进展,为阐明RA新的病理机制和发现新的药物靶点提供重要依据。

Rheumatoid arthritis(RA)is an autoimmune disease characterized by excessive activation of autoreactive T cells and B cells,abundant production of autoantibodies and multiple joint involvement.Under the influence of heredity and environment,the disorder of innate immunity and adaptive immunity is the fundamental cause of the disease.In recent years,with rapid development of immunometabolism,milestone has been made in regulating the differentiation and function of immune cells through different energy metabolism pathways and related molecules.Many studies have shown that Trp-IDO1,2/TDO2-Kyn metabolic pathway mediates the pathogenesis and development of autoimmune diseases such as RA.This review summarizes the role of tryptophan(Trp),kynurenine(Kyn)and other metabolites in this metabolic pathway,as well as the role of rate-limiting enzymes indoleamine 2,3-dioxygenase 1(IDO1),indoleamine 2,3-dioxygenase 2(IDO2)and tryptophan-2,3-dioxygenase 2(TDO2)in mediating RA inflammatory immune response and synovitis inflammation.This provides an important basis for elucidating the new pathological mechanism of RA and discovering new drug targets.