REGULATORY ROLE OF FC(EPSILON)RI IN ALLERGIC INFLAMMATION

最近的事态发展表明，重要的监管 肥大细胞的功能，包括向T细胞呈递抗原 细胞和诱导B细胞产生IgE。最近和 出乎意料的发现是Fc ε RI在人 朗格汉斯细胞、单核细胞和嗜酸性粒细胞表明， FCepsilonRI可能具有比以前更广泛的功能 相信。 本提案的主要目的是测试 假设FcepsilonRI在 肥大细胞的调节功能和具体目的是 以下内容： 1. 肥大细胞在抗原中作用的建立 演示文稿. 肥大细胞在抗原中的作用 通过Fc受体RI途径呈递给T细胞将是 考察 假设肥大细胞可以引导T细胞 将检测优先分化为Th 2亚群的细胞 并与其它抗原呈递细胞进行比较。 共刺激分子参与这一过程将 被确定。 FcepsilonRI在抗原提呈中的作用 也将通过体内实验证实。 2. FcepsilonRI在细胞凋亡调控中的作用 通过B细胞诱导IgE合成。 小鼠的能力 检查肥大细胞诱导B细胞合成IgE的能力。 参与肥大细胞/B细胞的细胞表面分子 互动将被识别。 FcepsilonRI在 这一过程将通过比较肥大细胞从 FcepsilonRI缺陷小鼠与正常小鼠相比， 以及通过使用可溶性FcepsilonRI作为 抑制剂. 肥大细胞活化与 将研究IgE合成的诱导。 的作用 肥大细胞Fc ε RI在可溶性抗原抗体应答中的作用 将被评估。 3. FcepsilonRI在变态反应中作用的建立 气道炎症 通过使用Fc ε RI缺陷小鼠，我们 将决定Fc受体介导的肥大细胞活化 对过敏原诱导的气道炎症至关重要。 的 肥大细胞活化对Th 1/Th 2分化影响 将对答复进行调查。 肺mst细胞的能力 将评估向T细胞呈递抗原的能力。 的能力 肺肥大细胞诱导B细胞IgE合成也将是 评估。 对肥大细胞功能的更全面了解，包括 由FcepsilonRI介导的，应促进发展 药物，针对抑制肥大细胞活性， 治疗过敏性炎症。

Recent developments have suggested important regulatory functions of mast cells, including presentation of antigen to T cells and induction of IgE production by B cells. The recent and unexpected finding that FcepsilonRI is expressed on human langerhans cells, monocytes and eosinophils have suggested that FcepsilonRI may have much broader functions than previously believed. The primary objective of this proposal is to test the hypothesis that FcepsilonRI plays a central role in the regulatory functions of mast cells and the Specific Aims are the following: 1. The establishment of the role of mast cells in antigen presentation. The effectiveness of mast cells in antigen presentation to T cells via the Fcepsilon RI pathway will be examined. The hypothesis that mast cells can direct T cells to differentiate preferentially to the Th2 subset will be tested and comparison will be made with other antigen presenting cells. The involvement of co-stimulatory molecules in this process will be determined. The role of FcepsilonRI in antigen presentation will also be confirmed by in vivo experiments. 2. The establishment of regulatory role of FcepsilonRI in induction of IgE synthesis by B cells. The ability of murine mast cells to induce IgE synthesis by B cells will be examined. Cell surface molecules that are involved in mast cell/B cell interactions will be identified. The role of FcepsilonRI in this process will be confirmed by comparing mast cells from FcepsilonRI-deficient mice with those from their normal littermates as well as by using soluble FcepsilonRI as an inhibitor. The relationship between mast cell activation and induction of IgE synthesis will be investigated. The role of mast cell FcepsilonRI in antibody responses to soluble antigens will be evaluated. 3. The establishment of the role of FcepsilonRI in allergic airway inflammation. By using FcepsilonRI-deficient mice, we will determine whether FcepsilonRI-mediated mast cell activation is critical for allergen-induced airway inflammation. The influence of mast cell activation on differential Th1/Th2 responses will be investigated. The ability of lung mst cells to present antigens to T cells will be evaluated. The ability of lung mast cells to induce B cell IgE synthesis will also be assessed. A fuller understanding of the functions of mast cells, including those mediated by FcepsilonRI, should facilitate the development of drugs, targeted at inhibition of mast cell activity, for the treatment of allergic inflammation.