Serum amyloid A inhibits dendritic cell differentiation by suppressing GM-CSF receptor expression and signaling

• Published in: Experimental & molecular medicine Vol. 49; no. 8; p. e369
• Main Authors: Kim, Ji Cheol, Jung, Young Su, Lee, Ha Young, Park, Joon Seong, Bae, Yoe-Sik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25-08-2017; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/250/232/2059; 631/80/86/2363; 96/31; Amyloid; Animals; Biomedical and Life Sciences; Biomedicine; CCAAT-Enhancer-Binding Proteins - genetics; CCAAT-Enhancer-Binding Proteins - metabolism; CD11c antigen; CD11c Antigen - genetics; CD11c Antigen - metabolism; Cell Differentiation; Cell surface; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; Granulocyte-macrophage colony-stimulating factor; Humans; Interleukin 4; Macrophages - metabolism; Male; Medical Biochemistry; Mice; Mice, Inbred C57BL; Molecular Medicine; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Original; original-article; Primary Cell Culture; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; PU.1 protein; Receptors, Formyl Peptide - genetics; Receptors, Formyl Peptide - metabolism; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Serum Amyloid A Protein - genetics; Serum Amyloid A Protein - metabolism; Stem Cells; T cell receptors; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-like receptors; Trans-Activators - genetics; Trans-Activators - metabolism
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2017.120

In this study, we report that an acute phase reactant, serum amyloid A (SAA), strongly inhibits dendritic cell differentiation induced by GM-CSF plus IL-4. SAA markedly decreased the expression of MHCII and CD11c. Moreover, SAA decreased cell surface GM-CSF receptor expression. SAA also decreased the expression of
PU.1
and
C/EBPα
, which play roles in the expression of GM-CSF receptor. This inhibitory response by SAA is partly mediated by the well-known SAA receptors, Toll-like receptor 2 and formyl peptide receptor 2. Taken together, we suggest a novel insight into the inhibitory role of SAA in dendritic cell differentiation.
Immunology: Regulating immune cell differentiation
Researchers in Korea have shown how a protein produced by the liver regulates how immune cells respond to injury or infection. Dendritic cells are white blood cells which play an important role in mammalian immune systems, presenting potentially dangerous antigens to T-cells and triggering a rapid response. Yoe-Sik Bae at Sungkyunkwan University and co-workers investigated how dendritic cell differentiation is affected by serum amyloid A (SAA), a protein produced by the liver in response to inflammation. Bae's team stimulated mouse bone marrow cells using the growth factor GM-CSF to generate fully functioning dendritic cells. When they repeated the experiment adding SAA, they found that SAA and its receptors inhibited dendritic cell differentiation from bone marrow cells by suppressing GM-CSF signalling. SAA may therefore mediate the body's immune response during infection or injury by suppressing dendritic cell activity.