High-Dimensional Profiling of Circulating Dendritic Cells and Monocytes in Atopic Dermatitis Patients by Mass Cytometry

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a multifactorial pathophysiology. Although AD has been characterized by a T helper type 2 cell response, the role of the myeloid populations in the pathogenesis of AD remains unclear. Methods: Peripheral blood mononuclear cells from 48 AD patients and 48 healthy controls were profiled using mass cytometry, primarily focusing on dendritic cells (DCs) and monocytes. Further analysis of a public single-cell RNA sequencing (scRNA-seq) dataset and immunofluorescence staining of lesional skin in AD were conducted for further validation. Results: The frequency of circulating cDC1 was significantly decreased in AD compared with healthy controls. The frequency of cDC1 was negatively correlated with disease severity scores and serum immunoglobulin E levels. The expression of FcεRIa was significantly increased in the DC populations, including cDC1, cDC2, plasmacytoid DC, and Axl+ DC. CD163, a marker of the inflammatory DC subset DC3, was increased in AD patients, suggesting an increased DC3 signature in AD patients. Analysis of a public scRNA-seq dataset further corroborated the decreased frequency of cDC1. The expression of cutaneous lymphocyte antigen was increased in cDC1 of AD compared with HC, suggesting increased migration of cDC1 to the skin. Aligned with this hypothesis, the frequency of cDC1 was shown to be increased in AD lesional skin using immunofluorescence staining. Conclusions: These results provide insight into the potential role of DC and monocyte populations in AD. We report decreased circulating cDC1 frequency and increased DC3 signature. The corresponding increased frequency of cDC1 in AD lesional skin implies their role in modulating AD pathophysiology.