Induction of IL-10+ CD4+ CD25+ regulatory T cells with decreased NF-κB expression during immunotherapy.
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.
Tsai
Yi-Giien
YG
Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.
Chiou
Ya-Ling
YL
Chien
Jien-Wen
JW
Wu
Han-Ping
HP
Lin
Ching-Yuang
CY
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage* / Q000009:adverse effects; D060829:Arthropod Proteins; D015704:CD4 Antigens / Q000096:biosynthesis; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D003888:Desensitization, Immunologic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007108:Immune Tolerance; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012129:Respiratory Function Tests; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015704:CD4 Antigens; C451163:Dermatophagoides pteronyssinus antigen p 2; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050838:Interferon Regulatory Factor-3; D053645:Interleukin-2 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D053592:Interleukin-1 Receptor-Associated Kinases