An Interleukin-4 and Interleukin-13 Induced Atopic Dermatitis Human Skin Equivalent Model by a Skin-On-A-Chip

• Published in: International journal of molecular sciences Vol. 23; no. 4; p. 2116
• Main Authors: Kim, Kyunghee, Kim, Hyeju, Sung, Gun Yong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-02-2022; MDPI
• Subjects: Animals; atopic dermatitis; Carbonic anhydrase; carbonic anhydrase II; Cell culture; Chemical compounds; Chip formation; Cytokines; Dermatitis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - metabolism; Eczema; Eczema - drug therapy; Eczema - metabolism; Eczema - pathology; Epidermis; Epidermis - drug effects; Epidermis - metabolism; Epidermis - pathology; Gene expression; Gene Expression - drug effects; Gene Expression - physiology; human skin equivalent; Humans; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; interleukin-13; Interleukin-13 - metabolism; interleukin-4; Interleukin-4 - metabolism; Keratin; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - pathology; Lab-On-A-Chip Devices; Membrane Proteins - pharmacology; Microfluidics; Morphology; Pharmacology; Protein expression; Proteins; Rats; Skin; Skin - drug effects; Skin - metabolism; Skin - pathology; skin-on-a-chip; carbonic anhydrase II; interleukin-4; atopic dermatitis; skin-on-a-chip; human skin equivalent; interleukin-13
• DOI: 10.3390/ijms23042116
• EISSN: 1422-0067
• ISSN: 1422-0067; 1661-6596

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
, 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.