The role of innate immune accessory cells in Th2 differentiation

Abstract

Allergy is a common syndrome that affects around around 1 billion people worldwide, with an increasing prevalence. The most common allergic manifestations are allergic rhinitis, atopic dermatitis, food allergy and allergic asthma. Allergy is mainly characterized by a type 2 immune response, with the differentiation of T helper (Th) cells into Th2 and high production of IgE. Although much is known about allergic immune effector mechanisms, little is known about the crucial mechanisms that lead to Th2 differentiation and allergic immune initiation. Dendritic cells initiate Th cell activation by providing antigen and costimulation. After cutaneous exposure to allergen dermal dendritic cells expressing CD301b are crucial for Th2 polarization, but they are not sufficient, indicating a possible role for an innate accessory cell in providing skewing signals. Any such accessory cell would be required to be present in draining lymph nodes, the site of Th cell activation, where it would produce a Th2-skewing signal. But the identity of that accessory cell as well as the skewing signal remains unknown. Many different cells have been postulated to play a role in Th2 skewing including basophils, eosinophils, mast cells and innate lymphoid cells, but there is conflicting data as to the role of each of these in Th2 skewing. Similarly, although different cytokines have been proposed to act as the main Th2-skewing signal, it is unclear what factor is necessary. This project aims to identify which Th2-skewing accessory cell type is responsible for inducing Th2 differentiation as well as the cytokines and chemokines responsible for its function. (AU)