Skin barrier dysfunction, a defining feature of atopic dermatitis (AD), arises from multiple interacting systems. In AD, skin inflammation is caused by host-environment interactions involving keratinocytes as well as tissue-resident immune cells such as type 2 innate lymphoid cells, basophils, mast cells, and T helper type 2 cells, which produce type 2 cytokines, including IL-4, IL-5, IL-13, and IL-31. Type 2 inflammation broadly impacts the expression of genes relevant for barrier function, such as intracellular structural proteins, extracellular lipids, and junctional proteins, and enhances Staphylococcus aureus skin colonization. Systemic anti‒type 2 inflammation therapies may improve dysfunctional skin barrier in AD.
Keywords: AD, atopic dermatitis; AMP, antimicrobial peptide; CLDN, claudin; FFA, free fatty acid; ILC2, type 2 innate lymphoid cell; Jaki, Jak inhibitor; K, keratin; KC, keratinocyte; MMP, matrix metalloproteinase; NMF, natural moisturizing factor; PAR, protease-activated receptor; PDE-4, phosphodiesterase-4; SC, stratum corneum; SG, stratum granulosum; TCI, topical calcineurin inhibitor; TCS, topical corticosteroid; TEWL, transepidermal water loss; TJ, tight junction; TLR, toll-like receptor; TNF-α, tumor necrosis factor alpha; TYK, tyrosine kinase; Th, T helper; ZO, zona occludens; hBD, human β-defensin.
© 2022 The Authors.