Insults from allergens or viruses trigger mucosal epithelial cells or skin cells (keratinocytes, fibroblasts, and mast cells) to produce TSLP. TSLP initiates the innate phase of allergic immune responses by activating immature DCs to produce the chemokines IL-8 and eotaxin-2, as well as the Th2-attracting chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), and by costimulating mast cells to produce IL-5 and IL-13, as well as GM-CSF and IL-6. TSLP-activated DCs mature and migrate into the draining lymph nodes to initiate the adaptive phase of allergic immune responses. TSLP-activated DCs express OX40L, which triggers the differentiation of allergen-specific naive CD4⁺ T cells into inflammatory Th2 cells that produce IL-4, IL-5, IL-13, and TNF-α but not IL-10. Inflammatory Th2 cells then migrate back to the site of inflammation because of the local production of TARC and MDC. The cytokines produced by the inflammatory Th2 cells (IL-4, IL-5, IL-13, and TNF-α) initiate allergic inflammation by triggering IgE and mucus production and eosinophilia. Figure modified with permission from J. Allergy Clin. Immunol. (25).