Indoleamine 2,3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines
Indoleamine 2,3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines
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DOI：
10.1038/sj.cr.7290282
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发表时间：
2005-03-01
期刊：
影响因子：
44.1
通讯作者：
Lin, CLS
中科院分区：
文献类型：
--
作者：
Hwang, SL;Chung, NPY;Lin, CLS
吲哚胺2，3-双加氧酶（IDO）是色氨酸催化剂的限速酶。在人和鼠细胞中，IDO在体外抑制抗原特异性T细胞增殖，并在鼠妊娠期间抑制T细胞对胎儿同种异体抗原的应答。在小鼠中，IDO表达是树突状细胞（DC）的特定亚群的可诱导特征，并且对于T细胞调节特性是重要的。然而，IDO和色氨酸剥夺对DC功能的影响仍然未知。我们在这里报告，当色氨酸利用被IDO的药理学抑制剂1-甲基色氨酸（1 MT）阻止时，由致病刺激脂多糖（LPS）或炎性细胞因子TNF-α诱导的DC活化在表型和功能上都被抑制。当DC被生理刺激物CD 40配体刺激时，这种作用不太显著。在DC活化过程中色氨酸剥夺也调节CCR 5和CXCR 4的表达，以及DC对趋化因子的反应。这些结果表明，色氨酸在微环境中的使用是必不可少的DC成熟，也可能在DC迁移行为的调节中发挥作用。
Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism. In human and murine cells, IDO inhibits antigen-specific T cell proliferation in vitro and suppresses T cell responses to fetal alloantigens during murine pregnancy. In mice, IDO expression is an inducible feature of specific subsets of dendritic cells (DCs), and is important for T cell regulatory properties. However, the effect of IDO and tryptophan deprivation on DC functions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1 MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflammatory cytokine TNF-alpha was inhibited both phenotypically and functionally. Such an effect was less remarkable when DC was stimulated by a physiological stimulus, CD40 ligand. Tryptophan deprivation during DC activation also regulated the expression of CCR5 and CXCR4, as well as DC responsiveness to chemokines. These results suggest that tryptophan usage in the microenvironment is essential for DC maturation, and may also play a role in the regulation of DC migratory behaviors.