Inhibitory effects of suplatast tosilate on the differentiation and function of monocyte-derived dendritic cells from patients with asthma

• Published in: Clinical and experimental allergy 2007-07, Vol.37 (7), p.1083-1089
• Main Authors: Tanaka, A., Minoguchi, K., Samson, K. T. R., Oda, N., Yokoe, T., Tazaki, T., Yamamoto, Y., Yamamoto, M., Ohta, S., Adachi, M.
• Format: Article
• Language: English
• Subjects: Anti-Allergic Agents - pharmacology; Anti-Allergic Agents - therapeutic use; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Antigens, CD - metabolism; Arylsulfonates - pharmacology; Arylsulfonates - therapeutic use; Asthma - drug therapy; Asthma - immunology; Biological and medical sciences; Case-Control Studies; CC chemokine ligand 17; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - drug effects; Cell Proliferation; Cell Survival - drug effects; Cells, Cultured; Chemokine CCL17; Chemokines, CC - metabolism; Coculture Techniques; dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; IL-10; IL-12; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Interleukin-12 Subunit p40 - metabolism; Interleukin-4 - metabolism; Interleukin-5 - metabolism; Lymphocyte Activation; Medical sciences; Monocytes - drug effects; Monocytes - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sulfonium Compounds - pharmacology; Sulfonium Compounds - therapeutic use; suplatast tosilate
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02616.x

Summary Background Dendritic cells (DCs) are antigen‐presenting cells that efficiently activate T cells. Objective We examined the effects of suplatast tosilate, which prevents T‐helper type 2 responses, on the differentiation and function of monocyte‐derived DCs (moDCs). Methods DCs were differentiated in vitro from peripheral monocytes from patients with asthma by the addition of granulocyte macrophage colony‐stimulating factor and IL‐4 in the presence or absence of suplatast tosilate. Cell surface molecules (CD1a, CD14, CD80, CD83, CD86, HLA‐DR) on immature and mature DCs were analysed with flow cytometry, and the secretion of CC chemokine ligand (CCL)17 (thymus and activation‐regulated chemokine), IL‐12p70, IL‐12p40, and IL‐10 was measured with an ELISA. We also studied the proliferative responses of allogeneic CD4+ T cells from healthy subjects to DCs differentiated in the presence of suplatast tosilate. In addition, the production of IFN‐γ and IL‐5 by CD4+ T cells after coculture with untreated DCs or suplatast tosilate‐treated DCs was measured with ELISA. Results Suplatast tosilate significantly inhibited the expression of CD1a, CD80, and CD86 on immature DCs and of CD1a, CD80, CD83, and CD86 on mature DCs. Suplatast tosilate also significantly inhibited the secretion of CCL17, IL‐12p70, and IL‐12p40; however, the secretion of IL‐10 was not affected. The proliferative responses of allogeneic CD4+ T cells to suplatast tosilate‐treated DCs were suppressed. Moreover, suplatast tosilate‐treated DCs had an impaired capacity to stimulate CD4+ T cells to produce IFN‐γ and IL‐5. Conclusion Suplatast tosilate inhibits the differentiation, maturation, and function of moDCs.