Role of epithelium and C type fibers in allergic inflammation

Abstract

Allergic responses are considered as cellular processes originated basically from the immune system. However, the dramatic rise in the prevalence of such disorders suggests a more complex phenomenon. Recent clinical and experimental evidences implicate both the epithelium and sensitive neurons, through C type fibers, directly in the development of allergic inflammation. Nevertheless, the cellular and molecular mechanisms responsible for this response are not well established. Therefore, the aim of this project is to investigate the role of epithelium cells as well as C fibers in allergen sensing and initiation of adaptive Th2 responses. For this, we will characterize the allergic inflammation in response to papain, a cysteine-protease, or phospholipase A2 from bee venom. The role of epithelium will be analyzed through tissue damage induced by these allergens and consequent release of pro-Th2 cytokines: IL-25, IL-33 e TSLP. The function of sensitive neurons will be evaluated in mice with depleted C type fibers. Within this perspective, we expect to generate a big picture of signaling pathways involved in Th2 responses considering the biology of epithelium cells and sensitive neurons. The proposal is original and innovative in nature as it aims to integrate the physiology of neurogenic inflammation and epithelium damage in allergen sensing. It provides, therefore, relevant clinical implications. (AU)