Immunologic pathways in AD. Th2 cells circulating in the peripheral blood of AD patients result in elevated serum IgE and eosinophils. These T cells express the skin homing receptor, CLA, and recirculate through unaffected AD skin where they can engage allergen-triggered IgE⁺ LCs and mast cells (MCs) that contribute to Th2 cell development. Skin injury by environmental allergens, scratching, or microbial toxins activates keratinocytes to release proinflammatory cytokines and chemokines that induce the expression of adhesion molecules on vascular endothelium and facilitate the extravasation of inflammatory cells into the skin. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) and DC-derived IL-10 also enhance Th2 cell differentiation. AD inflammation is associated with increased Th2 cells in acute skin lesions, but chronic AD results in the infiltration of inflammatory IDECs, macrophages (Mφ), and eosinophils. IL-12 production by these various cell types results in the switch to a Th1-type cytokine milieu associated with increased IFN-γ expression. Figure modified with permission from The Journal of Allergy and Clinical Immunology (35).