Abstract
Currently, the mechanism of progression of atopic dermatitis (AD) is not well understood because there is no physiologically appropriate disease model in terms of disease complexity and multifactoriality. Type 2 inflammation, mediated by interleukin (IL)-4 and IL-13, plays an important role in AD. In this study, full-thickness human skin equivalents consisting of human-derived cells were fabricated from pumpless microfluidic chips and stimulated with IL-4 and IL-13. The morphological properties, gene expression, cytokine secretion and protein expression of the stimulated human skin equivalent (HSE) epidermis were investigated. The results showed epidermal and spongy formations similar to those observed in lesions in AD, and decreased expression of barrier-related filaggrin, loricrin and involucrin genes and proteins induced by IL-4Rα signaling. In addition, we induced the expression of carbonic anhydrase II (CAII), a gene specifically expressed in the epidermis of patients with AD. Thus, AD human skin equivalents can be used to mimic the key pathological features of atopic dermatitis, overcoming the limitations of existing studies that rely solely on mouse models and have been unable to translate their effects to humans. Our results will be useful for future research on the development of therapeutic agents for atopic dermatitis.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with widespread barrier dysfunction and T helper 2 (Th2) cytokines [1,2]
Skin-on-a-chip (SOC), a microphysiological system technology in 3D culture, utilizes human skin equivalent (HSE), which has the same characteristics as human skin, as it allows drug screening to be performed quickly and [22,23]
Morphological changes in the AD-like HSE model were examined by hematoxylin and eosin (H&E) staining (Figure 2a–l)
Summary
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with widespread barrier dysfunction and T helper 2 (Th2) cytokines [1,2]. AD is an imbalance in the Th2 immune response where there is an increase in the gene expression levels of major Th2 cytokines during the acute phase [3,4]. It is characterized by dry erythema and severe itching. Acute AD exhibits spongiosis in the basal epidermal layer [5]. Atopic dermatitis in the chronic phase, lichenificated lesions, typically shows epidermal hyperplasia and parakeratotic hyperkeratosis. AD is likely caused by epidermal barrier alteration and Th2 immune response dysregulation [9,10]
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