Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients

Backgrounds: Invariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between blood Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthma in a mouse model.

Objective: We investigated whether FlaB modulates the function of blood iNKT cells in asthma patients.

Methods: Peripheral blood mononuclear cells (PBMCs) were treated with FlaB and then iNKT cells-derived and intracellular cytokines were determined by ELISA and flow cytometry, respectively, following the stimulation with a-galactosylceramide (a-GalCer). Foxp3⁺ iNKT cells were measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, CD14⁺monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma were co-cultured, in which intracellular cytokines of iNKT cells were determined. In some experiments, IL-10R mAb was used.

Results: FlaB treatment reduced the productions of IL-4 and IL-17 from iNKT cells in PBMCs cultures, which effects were ameliorated following the addition of IL-10R mAb. FlaB-treated DCs decreased the frequencies of IL4⁺ and IL-17⁺ iNKT cells, which effects were eliminated after the addition of IL-10R mAb. In contrast, Foxp3⁺iNKT cells were induced by FlaB treatment, which effect disappeared after the addition of IL-10R mAb.

Conclusion: FlaB may inhibit Th2- and Th17-like iNKT cells and enhance Foxp3⁺ iNKT cells via DCs in an IL-10-dependent fashion in asthma patients. In patients with asthma phenotype in association with iNKT cells, FlaB will be the effective immunomodulator for iNKT cell-based immunotherapy.