ABSTRACT
Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3
ABSTRACT
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.