Drug screening system development with high-throughput sequencing targeting skin-specific T cells in atopic dermatitis = Drug screening system development with high-throughput sequencing targeting skin-specific T cells in atopic dermatitis

다국어 초록 (Multilingual Abstract)

Atopic dermatitis (AD) is a common inflammatory skin disease, which has increased 2-3 times over the last century, especially in the developed countries. Specific treatments for AD are still limited and the most commonly used treatments are topical steroids and calcineurin inhibitors. Thus, we aimed to develop drug screening system targeting tissue-resident memory T (TRM) cells which have emerged as a major component of skin-specific T cells. CD69 + and CD103+ TRM cells have been observed to reside in the skin tissue of AD patients. In this study, we characterized immune and cell signaling signatures that exhibit significant expression in skin-specific T cells from AD patients using high-throughput sequencing techniques and selected candidate drugs, A, B, C. The MTT assay confirmed that CD69+ and CD103+ TRM cells were reduced by setting the appropriate drug concentration and confirming the effects of the drug on AD skin tissues. Then, we used the flaky tail mice, which essentially lack filaggrin, an important component of AD skin barrier. We developed house dust mite (HDM)- treated AD mouse model and evaluated drug effects on these AD mice. Epidermal thickening, hyperkeratosis, and inflammatory cell infiltration were observed in these mice. Finally, we validated the change of skin-specific T cells through flow cytometry and ELISA assays to evaluate skin-specific effects of the candidate drugs. This drug screening system targeting skin-specific T cells in AD may contribute to the development of new skin-targeted therapeutics in AD near future.