Cytokine Profiles In Asthma And Allergic Diseases

抗原提呈细胞（APC）需要提呈过敏原并激活过敏原特异性T细胞。一些APC群体表达高亲和力IgE受体（Fc ε RI），并且其表达可使抗原呈递效率提高1000倍。鉴于DC在过敏性免疫应答的起始中的关键重要性，我们试图检查人DC亚群的Fc ε RI表达。 因此，我们检测了DC1和DC2群体中的Fc受体RI表达，已知DC1和DC2群体分别偏向Th1和Th2应答。Fc ε RI由前体DC 1（pDC 1）和pDC 2细胞以及成熟组织DC 1和DC 2细胞表达。过敏性哮喘受试者的FcepsilonRI表达显著高于非过敏性对照。pDC 1和pDC 2的表达与血清IgE浓度高度相关。 在一项单独的研究中，我们通过使用奥马珠单抗（抗IgE）降低血清IgE浓度，进一步检查了Fc ε RI的DC表达与IgE的关系。在奥马珠单抗治疗变应性鼻炎患者的临床试验中，我们连续检测了pDC 1和pDC 2细胞中FcepsilonRI的表达。奥马珠单抗导致FcepsilonRI的pDC 1和pDC 2表达显著下降，而安慰剂组无显著变化。奥马珠单抗分别使pDC 1和pDC 2细胞的FcepsilonRI表达降低52%和83%。此外，FcepsilonRI表达的降低与血清IgE的降低高度相关，表明两个变量之间存在直接关系。这两项研究的结果都支持血清IgE是驱动DC表达Fc ε RI的主要因素的结论。这些数据支持直接靶向Fc ε RI表达的新型治疗方法将影响过敏原特异性免疫应答的致敏和效应阶段的概念。

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.