The tryptophan metabolite 3-hydroxyanthranilic acid suppresses T cell responses by inhibiting dendritic cell activation

作者：Lee Won Sik; Lee Soung Min; Kim Mi Kyoung; Park Sae Gwang; Choi Ii Whan; Choi Inhak; Joo Young Don; Park Sung Jae; Kang Sun Woo; Seo Su Kil^*

来源：International Immunopharmacology, 2013, 17(3): 721-726.

DOI：10.1016/j.intimp.2013.08.018

• Indoleamine 2,3-dioxygenase
• 3-Hydroxyanthranilic acid
• Dendritic cells

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.

• 出版日期2013-11