Figure 6. Allergen sensitization of the airways during the induction of allergic-type asthma.
Infection (bacterial and viral) and pollutants perturb the airway epithelium, which leads to initial danger signalling and activation of innate signalling receptors. This signalling causes airway epithelial cells (ECs) to secrete chemokines and leads to trafficking of immature dendritic cells (DCs) to the mucosal epithelium. These DCs respond to danger signals through pattern recognition receptors (PRRs), which leads to their maturation into competent antigen-presenting myeloid-type DCs. Allergen detection and processing by these activated DCs is mediated by the extension of cellular processes into the airways or by the capture of allergens that have breached the epithelium. Allergen-loaded DCs then drive T cell differentiation by migrating to local lymph nodes where they interact with naive T cells (TN) via the T cell receptor (TCR), major histocompatibility complex (MHC) class II and co-stimulatory molecules. DC activation and T helper 2 (TH2) cell maturation and migration into the mucosa are influenced by additional epithelial-derived cytokines and chemokines, including IL-25, IL-33, CC-chemokine ligand 17 (CCL17) and CCL22. CCR, CC-chemokine receptor; GM-CSF, granulocyte–macrophage colony-stimulating factor; mDC, mucosal DC; TNF, tumour necrosis factor; TSLP, thymic stromal lymphopoietin. Figure from Ref. 31, Nature Publishing Group.