SEMINAR

Unravelling atopic dermatitis and psoriasis using single cell Rnaseq

Seunghee Hong

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea

Atopic dermatitis (AD) and psoriasis are prevalent chronic inflammatory skin diseases primarily mediated by T cells, often managed with cytokine antagonists or broad immunosuppressive agents. While both conditions involve epidermal keratinocyte responses to T-cell cytokines affecting growth and differentiation, they share activated Th22 and Th1 pathways leading to increased IL-22 and IFNγ production. Despite these similarities, AD exhibits Th2-skewed inflammation, while psoriasis displays Th17-skewed inflammation. To unravel the immunological dysregulations of these disorders, we conducted single-cell RNA sequencing. Initially, we analyzed peripheral blood mononuclear cells (PBMCs) from 12 AD patients and 6 healthy controls to characterize the systemic immune cell landscape associated with AD. We noted an increase of ILC2s and decrease of overall dendritic cells (DCs). However specific DC subtypes were postulated exclusively in very severe AD cases, exhibiting distinct Th2-priming gene profiles, and were named as ‘Th2_DC,’ which displays a strong correlation with disease severity. Subsequently, we analyzed skin samples from psoriasis patients and healthy controls. We identified a substantial expansion of IL17-expressing Th17 cells in psoriatic skin, displaying tissue-resident characteristics. Furthermore, we observed an increased population of IL23-expressing monocytes in psoriasis-afflicted skin, likely triggered by chemokines released by adjacent endothelial cells. These findings emphasize the contribution of distinct immune cell subsets to the pathogenesis of these diseases, underscoring the necessity for further investigation into their potential as therapeutic targets.