Abstract
Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease. AD is typically characterized by skewed T helper (Th) 2 inflammation, yet other inflammatory profiles (Th1, Th17, Th22) have been observed in human patients. How cytokines from these different Th subsets impact barrier function in this disease is not well understood. As such, we investigated the impact of the canonical Th17 cytokine, IL-17A, on barrier function and protein composition in primary human keratinocytes and human skin explants. These studies demonstrated that IL-17A enhanced tight junction formation and function in both systems, with a dependence on STAT3 signaling. Importantly, the Th2 cytokine, IL-4 inhibited the barrier-enhancing effect of IL-17A treatment. These observations propose that IL-17A helps to restore skin barrier function, but this action is antagonized by Th2 cytokines. This suggests that restoration of IL-17/IL-4 ratio in the skin of AD patients may improve barrier function and in so doing improve disease severity.
Highlights
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by an overactive immune response to a host of environmental allergens and dry/itchy skin
These observations propose that IL-17A helps to restore skin barrier function, but this action is antagonized by Th2 cytokines
IL-13, IL-17A, IL-25, or TNF-α)wound and these cytokines weresubmerged shown to reduce the expression of observed they would have on TJIL-22, assembly during repair
Summary
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by an overactive immune response to a host of environmental allergens and dry/itchy skin. Important discoveries have demonstrated that AD develops in part from genetic, and/or acquired defects in the skin barrier. The overall hypothesis is that skin barrier defects allow resident immune cells to gain access to microbes, allergens, and irritants, resulting in a robust type 2 immune response that can be characterized by the tissue recruitment of T helper (Th) 2 cells. Epidermal barrier is mediated by two structural components, the stratum corneum (SC) and tight junctions (TJs). The essential role that epidermal TJs play in maintaining the skin barrier was demonstrated by the claudin (CLDN) 1 deficient mouse, which suffers from extensive transepidermal water loss and succumbs shortly after birth to severe dehydration [4].
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