Fig. 5.

The roles of the hippo and Notch pathways in AAS. Under stimulation by allergens, epithelial cells synthesize large amounts of proinflammatory cytokines (IL-25, IL-33, TSLP, etc.), thereby acting on innate lymphocytes (ILC2 cells) and DCs. Jag1 on DCs interacts with Notch receptors on T cells for Notch pathway induction. Notch transforms induced Tregs into Th2 and Th17 cells. Naive CD4 + cells affect Tfh cell class switch recombination by secreting IL-5, thus acting on B cells to induce plasma cells, which produce IgE. At the same time, Th2 cells secrete IL-4 and others to activate B cells to synthesize IgE, which interacts with IgE receptors on mast cells. In case the allergen invades the body again, it directly cross-links with IgE on the cell surface and releases a variety of active mediators, which trigger the clinical symptoms of asthma. Th17 cells are activated through the Hippo pathway; Th2 cells are activated through the Wnt pathway, and GDF-15 molecules are stimulated to act on ILC2 cells to enhance the expression of IL-13, although this remains controversial. Notch converts induced Tregs into Th2 and Th17 cells via hippo pathway-dependent mechanisms. IL interleukin, TSLP thymic stromal lymphopoietin, ILC2 group 2 innate lymphoid cell, DC dendritic cell, Jag1 jagged1