Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells.
Allergy Asthma Immunol Res
; 8(3): 206-15, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26922930
ABSTRACT
PURPOSE:
Invariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients.METHODS:
Peripheral blood mononuclear cells (PBMCs) were treated with FlaB, and the secreted and intracellular cytokines of iNKT cells were evaluated by using ELISA and flow cytometry, respectively, following stimulation with α-galactosylceramide. Foxp3⺠iNKT cells were also measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, we co-cultured CD14⺠monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma and analyzed intracellular cytokines in iNKT cells.RESULTS:
A reduction of IL-4 and IL-17 production by iNKT cells in PBMCs after FlaB treatment was alleviated following blocking of IL-10 signaling. A decrease in the frequencies of IL-4⺠and IL-17⺠iNKT cells by FlaB-treated DCs was reversed after blocking of IL-10 signaling. Simultaneously, an increase in Foxp3⺠iNKT cells induced by FlaB treatment disappeared after blocking of IL-10.CONCLUSIONS:
FlaB may inhibit Th2- and Th17-like iNKT cells and induce Foxp3⺠iNKT cells by DCs via an IL-10-dependent mechanism in asthmatic patients. In patients with a specific asthma phenotype associated with iNKT cells, FlaB may be an effective immunomodulator for iNKT cell-targeted immunotherapy.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article