Skip to main content
. 2016 Jun 6;2(2):17. doi: 10.3390/jof2020017

Figure 1.

Figure 1

A hypothetical working model to describe the roles of molecular and cellular elements of the local innate response to Aspergillus in driving T helper type 2 adaptive immunity in the airway exposed to fungal allergens. In the resting condition, IL-33 is stored in the nucleus of airway epithelial cells. Exposure to fungal allergens (prominently including fungal proteases) induce the extracellular release of IL-33 and production of IL-25 and TSLP by the airway epithelium. Autocrine secretion of ATP and uric acid likely play a role in regulating epithelial release of IL-33. IL-33, IL-25, and TSLP activate innate lymphoid type 2 cells (ILC2) to produce a large quantity of type 2 cytokines including IL-5, IL-13, IL-9, and amphiregulin. Type 2 cytokines drive differentiation of B cells to secrete IgE (thereby sensitizing mast cells and basophils as allergic effectors) and attracting and activating eosinophils. IL-33, IL-25, and TSLP also act upon dendritic and naïve T cells to drive CD4+ T cell differentiation to a Th2 response. Basophil-derived IL-4 may facilitate ILC2 production of cytokines. ILC2-derived IL-13 enhances antigen uptake and migration of dendritic cells and promotes proliferation and differentiation of Th2-type CD4+ T cells. In addition, ILC2s and Th2-type CD4+ T cells may interact directly to sustain production of type 2 cytokines. Abbreviations: Baso, basophils; DC, dendritic cells; TSLP, thymic stromal lymphopoietin; ATP, adenosine triphosphate; IL, interleukin. Modified with permission from [22].