Induction of IL‐10+ CD4+ CD25+ regulatory T cells with decreased NF‐κB expression during immunotherapy

Abstract

MyD88 is a major toll-like receptor (TLR) adaptor to activate NF-κB, which acts as a mater switch for allergic inflammation disease. Sterile hust dust extracts have been reported with TLR-dependent immunostimulatory activities. The aim of this study was to evaluate whether Dermatophagoides pteronyssinus (Der p) immunotherapy may increase IL-10+ CD4+ CD25+ T cells with modulating MyD88 signaling proteins, to decrease NF-κB expression. Peripheral blood mononuclear cells were isolated from patients before and after 1 yr of Der p immunotherapy, and also from matched control subjects. After 2 days of Der p-2 stimulation, intracellular IL-10 and Foxp3 expression of CD4(+) CD25(+) T cells were measured by flow-cytometry. The expression of IL-1 receptor-associated kinase (IRAK)-1 in cytoplasm and IFN-regulator factor-3 (IRF-3) with NF-κB/p65 in nuclei was determined by Western-blot analysis. Patients undergoing immunotherapy produced more soluble CD14, IL-10, and TGF-β that correlated with FEV(1) improvement (p < 0.05). In the immunotherapy group, the number of Foxp3+ CD4+ Treg cells increased more than the baseline status (25.06 ± 4.19 vs. 16.08 ± 3.54, p < 0.05). Additionally, increased IL-10 production with decreased IRAK-1 and NF-κB/p65 nuclear translocation was observed in sorted-purified Treg cells. IL-10(+) CD4(+) CD25(+) Treg cells may respond to Der p-2 and down-regulate NF-κB/p65 expression to maintain immune tolerance during immunotherapy.