Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Allergy (Copenhagen), 2024-06, Vol.79 (6), p.1584-1597

Ort / Verlag

Denmark: Blackwell Publishing Ltd

Erscheinungsjahr

2024

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. We analyzed blood samples from 12 patients with severe atopic dermatitis (EASI > 21) using single‐cell RNA sequencing. Additionally, we validated our findings with skin single‐cell spatial sequencing and flow cytometry. Our findings revealed a strong correlation between disease severity and the expansion of ILC2s and ISG‐monocytes. Conversely, the number of natural killer (NK) cells was decreased in the patients, and the expression of cytotoxic/effector molecules in NK cells was negatively correlated with disease severity. Moreover, our study identified severe AD‐dominant Th2‐DCs that exhibited features of Th2‐priming DC signals and interacted with Th2 cells residing in AD lesional skin.Abbreviations: AD, atopic dermatitis; DC, dendritic cell; DE_junction, dermis epidermis junction; EASI, eczema area and severity index; IL, interleukin; ILC2, group 2 innate lymphoid cell; IRF4, interferon regulatory factor 4; ISG, interferon‐stimulated genes; MO, monocyte; NK, natural killer cell; STAT6, signal transducer and activator of transcription 6; TNFR, tumor necrosis factor receptor.