期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 17, 期 3, 页码 721-726出版社
ELSEVIER
DOI: 10.1016/j.intimp.2013.08.018
关键词
Indoleamine 2,3-dioxygenase; 3-Hydroxyanthranilic acid; Dendritic cells
资金
- Basic Science Research program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [NRF-2011-0010929]
- Inje University
The generation of typtophan (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-alpha 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. (C) 2013 Elsevier B.V. All rights reserved.
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