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.

Dendritic cells modifi cation during sublingual immunotherapy in children with allergic symptoms to house dust mites

“…This fi nding is supported by previous studies demonstrating that SLIT increases IL-10 production in PBMCs of allergic patients. [29][30][31][32] In particular, in the study by Ciprandi et al, [29] IL-10 production was induced by Dermatophagoides Farinae, but also by recall antigens and phytohemagglutinin, thereby raising the possibility that some IL-10 secreting cells were not T lymphocytes.…”

Subsets of regulatory T cells and their roles in allergy

“…Dermatophagoides pteronyssinus (Der p) immunotherapy causes increased numbers of Foxp3+ CD4+ Tregs, and elevated IL-10 production with decreased IRAK-1 and NF-κB/p65 nuclear translocation. IL-10(+) Tregs may respond to Der p-2 and down-regulate NF-κB/p65 expression in peripheral blood mononuclear cells to maintain immune tolerance during immunotherapy [66]. …”

Functional defects of CD46-induced regulatory T cells to suppress airway inflammation in mite allergic asthma

“…After electrophoresis, protein levels of nuclear NF-kB/p65, phosphor-AKT by western blot as previously described. 5 …”

“…Some studies indicate IL-10 inhibiting NF-kB translocation, thus relieving airway inflammation. 5,47,48 IL-10-producing Tr1 cells have an important role in the pathogenesis and treatment of allergic asthma. 28,49 Ni Choileain et al 50 demonstrated surface CD46 as cleaved by a metalloproteinase upon T-cell activation.…”

“…[1][2][3] Attention has focused on defects of natural occurring CD4 þ CD25 þ Treg cells that regulate inflammatory response in asthmatic. 4,5 Adaptive regulatory T (Tr1) cells secreting immunosuppressive cytokines may have a key role in maintaining immune tolerance to allergen in asthma. 6,7 For recruiting allergen-specific T cells to the lungs, the expression of specific adhesion proteins and chemokine receptors is vital.…”