Mapping the immune cell landscape of severe atopic dermatitis by single-cell RNA-seq

Seon Pil Jin, Kyungchun Lee, Yoon Ji Bang, Yun Hui Jeon, Sunyoung Jung, So Jung Choi, Ji Su Lee, Junhan Kim, Emma Guttman-Yassky, Chung Gyu Park, Hyun Je Kim, Seunghee Hong, Dong Hun Lee

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1584-1597
Number of pages14
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume79
Issue number6
DOIs
StatePublished - Jun 2024

Keywords

  • atopic dermatitis
  • chronic inflammatory disease
  • innate immunity
  • severe atopic dermatitis
  • single-cell RNA-Seq

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