Immune Netw.  2018 Oct;18(5):e35. 10.4110/in.2018.18.e35.

Aryl Hydrocarbon Receptor Ligands Indoxyl 3-sulfate and Indole-3-carbinol Inhibit FMS-like Tyrosine Kinase 3 Ligand-induced Bone Marrow-derived plasmacytoid Dendritic Cell Differentiation

• Hwang WB
• Kim DJ
• Oh GS
• Park JH

• KMID: 2424201
• DOI: http://doi.org/10.4110/in.2018.18.e35

Abstract

Aryl hydrocarbon receptor (AhR) regulates both innate and adaptive immune responses by sensing a variety of small synthetic and natural chemicals, which act as its ligands. AhR, which is expressed in dendritic cells (DCs), regulates the differentiation of DCs. However, effects of AhR on the differentiation of DCs are variable due to the heterogeneity of DCs in cell surface marker expression, anatomical location, and functional responses. The plasmacytoid DCs (pDCs), one of DC subsets, not only induce innate as well as adaptive immune responses by secreting type I interferons and pro-inflammatory cytokines, but also induce IL-10 producing regulatory T cell or anergy or deletion of antigen-specific T cells. We showed here that AhR ligands indoxyl 3-sulfate (I3S) and indole-3-carbinol (I3C) inhibited the development of pDCs derived from bone marrow (BM) precursors induced by FMS-like tyrosine kinase 3 ligand (Flt3L). I3S and I3C downregulated the expression of signal transducer and activator of transcription 3 (STAT3) and E2-2 (Tcf4). In mice orally treated with I3S and I3C, oral tolerance to dinitrofluorobenzene was impaired and the proportion of CD11c⁺B220⁺ cells in mesenteric lymph nodes was reduced. These data demonstrate that AhR negatively regulates the development of pDCs from BM precursors induced by Flt3L, probably via repressing the expression of STAT3.

Keyword

Plasmacytoid dendritic cells; Aryl hydrocarbon receptor; Cell differentiation; Signal transducer and activator of transcription 3; Immune tolerance; Tcf4

MeSH Terms

Animals
Bone Marrow
Cell Differentiation
Cytokines
Dendritic Cells*
Dinitrofluorobenzene
fms-Like Tyrosine Kinase 3*
Immune Tolerance
Interferon Type I
Interleukin-10
Ligands*
Lymph Nodes
Mice
Population Characteristics
Receptors, Aryl Hydrocarbon*
STAT3 Transcription Factor
T-Lymphocytes
Vascular Endothelial Growth Factor Receptor-1*
Cytokines
Dinitrofluorobenzene
Interferon Type I
Interleukin-10
Ligands
Receptors, Aryl Hydrocarbon
STAT3 Transcription Factor
Vascular Endothelial Growth Factor Receptor-1
fms-Like Tyrosine Kinase 3