title: The tryptophan metabolite 3-hydroxyanthranilic acid suppresses T cell responses by inhibiting dendritic cell activation.
abstract: The generation of tryptophan (Trp) metabolites by indoleamine 2,3-dioxygenase (IDO) is an effective mechanism for T cell suppression. However, the effect of Trp metabolites on dendritic cells (DCs) remains unclear. Here, we investigated whether the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) directly inhibits DC activation and is responsible for T cell suppression. We found that 3-HAA treatment significantly reduced IL-12, IL-6, and TNF-α production in bone marrow-derived DCs (BMDCs) stimulated with LPS. Maturation markers CD40, CD80, CD86, and I-A were also significantly reduced. Moreover, treatment with 3-HAA decreased the ability of DCs to stimulate T cell activation and differentiation in vitro and in vivo. Finally, we observed that phospho-JNK and phospho-38 levels were reduced in 3-HAA-treated DC2.4 cells and BMDCs. These results suggest that the tryptophan metabolite 3-HAA suppresses T cell responses by inhibiting DC activation.
authors.affiliation: Department of Hemato/Oncology, Busan Paik Hospital, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Soung-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.forename: Ii-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Inhak
authors.initials: I
authors.lastname: Choi
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Sung-Jae
authors.initials: SJ
authors.lastname: Park
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Kang
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D015095:3-Hydroxyanthranilic Acid; D014364:Tryptophan; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: 3-Hydroxyanthranilic acid; Dendritic cells; Indoleamine 2,3-dioxygenase