Non-lesional AD skin lesions show some immune infiltrates that produce inflammatory mediators, which might contribute to a defective epidermal barrier. Barrier defects lead to penetration by epicutaneous antigens that encounter Langerhans cells in the epidermis and dermal dendritic cells in the dermis, inducing marked immune activation and recruitment of inflammatory cells in acute AD lesions. Marked activation of Th2 and Th22 axes occurs in acute disease onset. Smaller increases in Th1 and Th17 immune axes were found in acute lesions. A progressive activation of Th2 and Th22, as well as Th1 pathways is characteristic of the chronic stage of AD. The relative induction of each T-cell subset, according to disease stage, is represented pictorially by their size, relative to the other T-cell subsets. Cytokines (i.e. IL-4, IL-13) and chemokines [i.e. CCL17, CCL18, CCL19, CXCL9, CXCL10, CXCL11] produced by various T-cells and DCs induce further activation and recruitment of additional immune cells. With the onset of acute disease, Th22 cells release IL-22, which induces epidermal hyperplasia, and synergistically with the Th17 cytokine, IL-17, drives an abrupt increase in a subset of terminal differentiation genes, specifically S100A7, S100A8 and S100A9 proteins. The increases in these barrier proteins contrast with the uniformly disrupted epidermal differentiation gene products (filaggrin, loricrin, corneodesmosin, etc.) throughout non-lesional, acute and chronic AD skin. The Th2 and Th22 cytokines contribute to inhibition of the terminal differentiation proteins. IL-31 is abruptly up-regulated in acute disease, potentially reflecting its role as an itch mediator in AD.
