Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway.

Abstract

Dendritic cells (DCs) are known as antigen-presenting cells and play a central role in both innate and acquired immunity. Peripheral blood monocytes give rise to resident and recruited DCs in lymph nodes and non-lymphoid tissues. The ligands of nuclear hormone receptors can modulate DC differentiation and so influence various biological functions of DCs. The role of bile acids (BAs) as signalling molecules has recently become apparent, but the functional role of BAs in DC differentiation has not yet been elucidated. We show that DCs derived from human peripheral blood monocytes cultured with a BA produce lower levels of interleukin-12 (IL-12) and tumour necrosis factor-α in response to stimulation with commensal bacterial antigens. Stimulation through the nuclear receptor farnesoid X (FXR) did not affect the differentiation of DCs. However, DCs differentiated with the specific agonist for TGR5, a transmembrane BA receptor, showed an IL-12 hypo-producing phenotype. Expression of TGR5 could only be identified in monocytes and was rapidly down-regulated during monocyte differentiation to DCs. Stimulation with 8-bromoadenosine-cyclic AMP (8-Br-cAMP), which acts downstream of TGR5 signalling, also promoted differentiation into IL-12 hypo-producing DCs. These results indicate that BAs induce the differentiation of IL-12 hypo-producing DCs from monocytes via the TGR5-cAMP pathway.

• Authors: Riko Ichikawa, Tetsuro Takayama, Kazuaki Yoneno, Nobuhiko Kamada, Mina T Kitazume, Hajime Higuchi, Katsuyoshi Matsuoka, Mitsuhiro Watanabe, Hiroshi Itoh, Takanori Kanai, Tadakazu Hisamatsu, Toshifumi Hibi
• Journal: Immunology (Immunology) Vol. 136 Issue 2 Pg. 153-62 (Jun 2012) ISSN: 1365-2567 [Electronic] England
• PMID: 22236403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

Chemical References

• Bile Acids and Salts
• GPBAR1 protein, human
• Receptors, G-Protein-Coupled
• Tumor Necrosis Factor-alpha
• Interleukin-12
• 8-Bromo Cyclic Adenosine Monophosphate

Topics

• 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
• Bile Acids and Salts (immunology, metabolism)
• Cell Differentiation (drug effects, immunology)
• Cells, Cultured
• Dendritic Cells (immunology, metabolism)
• Down-Regulation
• Humans
• Interleukin-12 (biosynthesis, immunology)
• Leukocytes, Mononuclear (immunology, metabolism)
• Receptors, G-Protein-Coupled (agonists, immunology)
• Tumor Necrosis Factor-alpha (biosynthesis, immunology)