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Indoleamine 2,3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines

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Cell Research 2005年第3期15卷 167-175页

作者： shih ling hwang,nancy pei-yee chung,jacqueline kwai-yi chan,chen-lung steve lin Department of Surgery Kaohsiung Medical University Kaohsiung Taiwan China Department of Surgery The University of Hong Kong Medical Centre Queen Mary Hospital Pokfulam Road Hong KongSAR China Department of Surgery The University of Hong Kong Medical Centre Queen Mary Hospital Pokfulam Road Hong KongSAR China Department of Surgery The University of Hong Kong Medical Centre Queen Mary Hospital Pokfulam Road Hong KongSAR China

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 func- tions remains unknown. We report here that when tryptophan utilization was prevented by a pharmacological inhibitor of IDO, 1-methyl tryptophan (1MT), DC activation induced by pathogenic stimulus lipopolysaccharide (LPS) or inflam- matory cytokine TNF-α 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 regu- lated 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.

关键词： Indoleamine 2 3-dioxygenase (IDO) dendritic cells activation T cell tryptophan chemokine.

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