Analysis of allergen-specific tolerance induction in patients suffering from type I allergies

花粉过敏经常与食物过敏有关，桦树花粉食物综合征就是一个例子。针对花粉过敏的特定免疫疗法通常不能影响相关的食物过敏，到目前为止还没有开发出标准的治疗方法。在应用项目中，我们打算分析人类耐受性树突状细胞对桦树花粉过敏患者与榛子过敏相关的免疫反应的影响。我们将使用成熟的人类耐受性IL-10调节的DC模型来研究Bet v 1(桦树的主要过敏原)和Cor a 1(榛子的主要过敏原)负载的耐受性DC诱导的T细胞反应，以开发I型过敏症的创新治疗方法。在我们的项目中，我们将分析IL-10dc对调节性T细胞的诱导，重点是抑制T细胞的发展，以交叉耐受的形式抑制花粉和食物过敏原特异性T细胞的反应。体外研究将深入了解过敏原特异性交叉耐受的潜在免疫机制。此外，使用过敏患者的PMBC重建的免疫缺陷小鼠的人源化模型，我们将在体内评估耐受性IL-10 DC和iTregs对所产生的过敏原特异性交叉耐受的T细胞反应的影响。这项研究的结果可能会为I型过敏，特别是与花粉相关的食物过敏开发新的预防或治疗方法。

Pollen-allergies are frequently related to food allergies as demonstrated for the birch pollen-food syndrome. Specific immunotherapy, well established for the treatment of pollen-allergies, often failed to affect the associated food allergy and no standard therapeutic approach has been developed so far. In the applied project, we intend to analyse the effect of human tolerogenic DC on the immune response of birch pollen allergics with associated hazelnut allergy. We will use the well-established model of human tolerogenic IL-10-modulated DC to investigate T cell responses induced by Bet v 1 (major allergen of birch) and Cor a 1 (major allergen of hazelnut) loaded tolerogenic DC for the development of an innovative treatment of type I allergies. In our project, we will analyse the induction of regulatory T cells by IL-10DC with focus on the development of suppressor T cells inhibiting both pollen as well as food allergen-specific T cell responses in form of cross-tolerance. In vitro investigation will give insights into the underlying immune mechanisms of the allergen-specific cross-tolerance. In addition, using a humanized model of immunodeficient mice reconstituted with PMBC from allergic patients, we will evaluate the effect of tolerogenic IL-10 DC and iTregs on the resulting T cell response with respect to allergen-specific cross-tolerance in vivo. The results of this study might allow for the development of novel preventive or therapeutic approaches for type I allergies and particularly for pollen-related food allergies.