Role of epithelial barrier function in food-induced anaphylaxis

上皮屏障功能在食物过敏反应中的作用 摘要 食物过敏是一个日益严重的公共卫生问题，大约有1500万人受到影响 美国。在过敏性食物疾病中，肥大细胞上的IgE与摄入的抗原结合，导致 肥大细胞的激活和脱颗粒。为了激活肥大细胞，食物抗原必须 穿过肠道上皮屏障，激活固有层中的细胞。交叉口 黏附分子-A(JAM-A)是一种紧密连接的跨膜蛋白，在 上皮细胞和内皮细胞屏障功能的维持。在小肠中，Jam-A有 被证明在上皮屏障功能中很重要，缺乏JAM-A的小鼠(JAM-A-/-) 会增加肠道通透性。这些Jam-A-/-老鼠会患上严重的食物过敏症 与WT动物相比，小鼠固有层中的肥大细胞增多 肠道，以及这些细胞的激活增加。在这项建议中，我们的目标是更好地 了解JAM-A在严重食物过敏发生中的作用，包括诱导 一种强烈的Th2反应，导致肥大细胞在小肠中聚集。我们进一步 计划以易感动物的肥大细胞为靶点，目的是减少过敏 回应。为此，我们将中和干细胞因子(SCF)，这是一种细胞因子，是 外周组织肥大细胞的生长和激活。我们假设中和SCF将会 防止肥大细胞堆积，防止严重过敏反应。这些 实验将有助于我们理解屏障在食物过敏反应中的作用，如 并提供了一种潜在的方法来减少这些反应 失调的屏障。

Role of epithelial barrier function in food-induced anaphylaxis ABSTRACT Food allergy is a growing public health problem with approximately 15 million people affected in the United States. In allergic food disease, IgE on mast cells bind to ingested antigens leading to the activation and degranulation of mast cells. In order to activate mast cells, food antigens must pass through the intestinal epithelial barrier and activate cells in the lamina propria. Junction Adhesion Molecule-A (JAM-A) is a tight junction transmembrane protein that plays a major role in the maintenance of barrier function in epithelia and endothelia. In the small intestine, JAM-A has been shown to be important in epithelial barrier function, and mice that lack JAM-A (JAM-A-/-) have increased intestinal permeability. These JAM-A-/- mice develop severe food allergic disease compared to WT animals and have increased mast cells in the lamina propria of the small intestine, as well as increased activation of these cells. In this proposal, we aim to better understand the role of JAM-A in the development of severe food allergy, including the induction of a strong Th2 response that results in mast cell accumulation in the small intestine. We further plan to target those mast cells in susceptible animals with the aim of decreasing the allergic response. To do this, we will neutralize stem cell factor (SCF), a cytokine that is required for the growth and activation of peripheral tissue mast cells. We hypothesize that neutralizing SCF will prevent mast cell accumulation and protect from severe anaphylactic reactions. These experiments will contribute to our understanding of barrier function in food allergic reactions, as well as provide a potential method for decreasing these reactions in the presence of a dysregulated barrier.