Indoleamine 2, 3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines.
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 (1MT), 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.
Hwang
Shin Ling
SL
Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan, China.
Chung
Nancy Pei-Yee
NP
Chan
Jacqueline Kwai-Yi
JK
Lin
Chen-Lung Steve
CL
D019013:CD40 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000502:physiology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019013:CD40 Antigens; C095085:CXCR5 protein, human; D018925:Chemokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; D014364:Tryptophan