한빛사논문
연세대학교
Seon-Pil Jin 1,2,3, Kyungchun Lee 4,5, Yoon Ji Bang 6, Yun-Hui Jeon 1,3, Sunyoung Jung 6, So-Jung Choi 6, Ji Su Lee 1,3, Junhan Kim 4,5, Emma Guttman-Yassky 7, Chung-Gyu Park 6,8,9, Hyun Je Kim 6,8,9,10, Seunghee Hong 4,5, Dong Hun Lee 1,2,3
1Department of Dermatology, Seoul National University Hospital, Seoul, Korea.
2Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
3Institute of Human-Environmental Interface Biology, Medical Research Center, Seoul National University, Seoul, Korea.
4Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
5Brain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University, Seoul, Korea.
6Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
7Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, USA.
8Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.
9Seoul National University Hospital, Seoul, Korea.
10Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
Seon-Pil Jin and Kyungchun Lee contributed equally to this article.
CORRESPONDING AUTHORS: Hyun Je Kim, Seunghee Hong, Dong Hun Lee
Abstract
Background: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial.
Methods: Employing single-cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls.
Results: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2-priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials.
Conclusion: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation.
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