Cytokine Profiles In Asthma And Allergic Diseases

抗原提呈细胞(APC)需要递呈变应原并激活变应原特异性T细胞。某些APC群体表达高亲和力的IgE受体(FcepsilonRI)，其表达可使抗原提呈效率提高1000倍。鉴于树突状细胞在启动变态反应性免疫反应中的关键作用，我们试图通过人树突状细胞亚群来检测FcepsilonRI的表达。 因此，我们研究了FcepsilonRI在DC1和DC2群体中的表达，这两个群体已知分别倾向于Th1和Th2反应。FcepsilonRI在前体细胞DC1(PDC1)和pDC2细胞以及成熟组织DC1和DC2细胞中均有表达。过敏性哮喘受试者FcepsilonRI的表达显著高于非特应性对照组。FcepsilonRI的pDC1和pDC2的表达与血清IgE浓度高度相关。 在另一项单独的研究中，我们通过使用奥马利单抗(抗IgE)降低血清IgE浓度，进一步研究了FcepsilonRI的DC表达与IgE的关系。在奥马珠单抗治疗变应性鼻炎的临床试验中，我们连续检测了pDC1和pDC2细胞中FcepsilonRI的表达。奥马珠单抗导致FcepsilonRI的pDC1和pDC2表达显著下降，而安慰剂组没有显著变化。奥马珠单抗可使pDC1和pDC2细胞FcepsilonRI的表达分别降低52%和83%。此外，FcepsilonRI表达的下降与血清IgE的下降高度相关，这表明这两个变量之间存在直接关系。两项研究的结果均支持血清IgE是DC表达FcepsilonRI的主要因素的结论。这些数据支持这样的概念，即直接针对FcepsilonRI表达的新治疗方法将影响过敏原特异性免疫反应的敏化和效应阶段。

Antigen presenting cells (APCs) are required to present allergen and activate allergen specific T cells. Some populations of APCs express the high affinity IgE receptor (FcepsilonRI) and its expression can increase the efficiency of antigen presentation by 1000-fold. Given the critical importance of DCs in the initiation of allergic immune responses, we sought to examine FcepsilonRI expression by human DC subsets. We thus examined FcepsilonRI expression in the DC1 and DC2 populations, which are known to bias towards a Th1 and Th2 response, respectively. FcepsilonRI was expressed by both the precursor DC1 (pDC1) and pDC2 cells, as well as by mature tissue DC1 and DC2 cells. FcepsilonRI expression was significantly greater in allergic asthmatic subjects than in non-atopic controls. pDC1 and pDC2 expression of FcepsilonRI was highly correlated to serum IgE concentration. In a separate study, we further examined the relationship of DC expression of FcepsilonRI to IgE by dropping serum IgE concentration through the use of omalizumab (anti-IgE). During a clinical trial of omalizumab in allergic rhinitis subjects we serially examined FcepsilonRI expression in pDC1 and pDC2 cells. Omalizumab caused a significant drop in both pDC1 and pDC2 expression of FcepsilonRI, whereas there was no significant change in the placebo group. Omalizumab decreased FcepsilonRI expression by 52% and 83% for pDC1 and pDC2 cells, respectively. Furthermore, the decrease in FcepsilonRI expression was highly correlated with the drop in serum IgE, suggesting a direct relationship between the two variables. The results of both studies support the conclusion that serum IgE is a major factor driving FcepsilonRI expression by DCs. These data support the concept that novel therapeutic approaches directly targeted at FcepsilonRI expression would affect both the sensitization and effector phases of the allergen specific immune response.