3,3'-Diindolylmethane Inhibits Flt3L/GM-CSF-induced-bone Marrow-derived CD103+ Dendritic Cell Differentiation Regulating Phosphorylation of STAT3 and STAT5.
- Author:
Joo Hung PARK
1
;
Ah Jeong CHOI
;
Soo Ji KIM
;
So Yeon JEONG
Author Information
- Publication Type:Original Article
- Keywords: AhR; Oral tolerance; 3,3'-diindolylmethane; CD103+ DC; Foxp3+ Tregs; STAT5
- MeSH: Animals; Bone Marrow Cells; Dendritic Cells*; Granulocyte-Macrophage Colony-Stimulating Factor; Immune System; Intestines; Ligands; Mice; Phosphorylation*; Phytochemicals; Receptors, Aryl Hydrocarbon; Transcription Factors
- From:Immune Network 2015;15(6):278-290
- CountryRepublic of Korea
- Language:English
- Abstract: The intestinal immune system maintains oral tolerance to harmless antigens or nutrients. One mechanism of oral tolerance is mediated by regulatory T cell (Treg)s, of which differentiation is regulated by a subset of dendritic cell (DC)s, primarily CD103+ DCs. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating immunity. The intestines are exposed to various AhR ligands, including endogenous metabolites and phytochemicals. It was previously reported that AhR activation induced tolerogenic DCs in mice or in cultures of bone marrow-derived DCs. However, given the variety of tolerogenic DCs, which type of tolerogenic DCs is regulated by AhR remains unknown. In this study, we found that AhR ligand 3,3'-diindolylmethane (DIM) inhibited the development of CD103+ DCs from mouse bone marrow cells stimulated with Flt3L and GM-CSF. DIM interfered with phosphorylation of STAT3 and STAT5 inhibiting the expression of genes, including Id2, E2-2, IDO-1, and Aldh1a2, which are associated with DC differentiation and functions. Finally, DIM suppressed the ability of CD103+ DCs to induce Foxp3+ Tregs.
