Effects of antiasthmatic agents on the functions of peripheral blood monocyte–derived dendritic cells from atopic patients

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• 作者：Sachiko Saeki ; Hiroto Matsuse ; Yuki Kondo ; Ikuko Machida ; Tetsuya Kawano ; Shinya Tomari ; Yasushi Obase ; Chizu Fukushima ; Shigeru Kohno
• 关键词：Monocyte-derived dendritic cell ; cysteinyl leukotriene ; cytokine ; cysteinyl leukotriene 1 receptor antagonist ; dexamethasone ; tacrolimus
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2004
• 出版时间：September 2004
• 年：2004
• 卷：114
• 期：3
• 页码：538-544
• 全文大小：239 K

文摘

Dendritic cells (DCs), the antigen-presenting cells in the airway, play a critical role in asthma. Nevertheless, there is little information on the effects of antiasthmatic agents on DCs.

Objectives

The purpose of the present study was to determine the effects of representative antiasthmatic agents, including cysteinyl leukotriene (cysLT) 1 receptor antagonists, corticosteroid, and tacrolimus, on DCs in inducing allergy.

Methods

Human peripheral blood monocyte–derived DCs (MoDCs) generated from atopic and healthy subjects were pulsed with Dermatophagoides farinae allergen in the presence of medium alone, pranlukast, montelukast, dexamethasone, or tacrolimus. The mRNA expressions of cysLT receptor, cysLTs producing enzymes, and various surface markers on MoDCs, as well as the concentrations of cysLTs, IL-10, and IL-12 in cultured supernatants, were determined. MoDCs were also cocultured in vitro with autologous CD4⁺ T cells, and IL-5 and IFN-γ production was measured.

Results

MoDCs of atopic patients expressed mRNAs of cysLT1 receptor and cysLT-producing enzymes, and allergen pulsing significantly increased cysLT production. MoDCs of atopic patients showed a T_H2-favoring phenotype and induced T_H2-skewed cytokine production from autologous CD4⁺ T cells. Dexamethasone and tacrolimus inhibited allergen-pulsed MoDC-induced cytokine production by autologous CD4⁺ T cells without and with IL-10 inhibition, respectively. CysLT1 receptor antagonists had no effect on MoDC functions.

Conclusion

Our results indicate that MoDCs of atopic patients induce a T_H2 reaction. Corticosteroid and tacrolimus, but not cysLT1 receptor antagonists, inhibit T_H2 reactions, and this effect is probably mediated through different pathways.