Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.
Pediatr Allergy Immunol. 2010 Feb;21(1 Pt 2):e166-73. doi: 10.1111/j.1399-3038.2009.00870.x. Epub 2009 Aug 13.
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.
MyD88 是一种主要的 Toll 样受体 (TLR) 衔接子，可激活 NF-κB，NF-κB 作为过敏炎症疾病的主要开关。已报道无生命的尘螨提取物具有 TLR 依赖性免疫刺激活性。本研究旨在评估粉尘螨 (Der p) 免疫疗法是否可以通过调节 MyD88 信号蛋白增加 IL-10+CD4+CD25+T 细胞，从而降低 NF-κB 的表达。从接受 Der p 免疫治疗 1 年后的患者和匹配的对照者中分离外周血单个核细胞。在 Der p-2 刺激 2 天后，通过流式细胞术测量 CD4+CD25+T 细胞内的 IL-10 和 Foxp3 表达。通过 Western blot 分析测定细胞质中的白细胞介素 1 受体相关激酶 (IRAK)-1 和核中的干扰素调节因子-3 (IRF-3)与 NF-κB/p65 的表达。接受免疫治疗的患者产生更多的可溶性 CD14、IL-10 和 TGF-β，这与 FEV1 的改善相关 (p<0.05)。在免疫治疗组中，Foxp3+CD4+Treg 细胞的数量比基线水平增加更多 (25.06±4.19 对 16.08±3.54，p<0.05)。此外，在分选纯化的 Treg 细胞中观察到 IL-10 产生增加，同时 IRAK-1 和 NF-κB/p65 核易位减少。IL-10+CD4+CD25+Treg 细胞可能对 Der p-2 作出反应，并下调 NF-κB/p65 的表达，以在免疫治疗期间维持免疫耐受。
