Abstract
Mononuclear phagocytes (MPs) are important immune regulatory cells in atopic dermatitis (AD). We previously identified 6-sulfo LacNAc-expressing monocytes (slanMo) as TNF-α- and IL-23-producing cells in psoriatic skin lesions and as inducers of IFN-γ-, IL-17-, and IL-22-producing T cells. These cytokines are also upregulated in AD and normalize with treatment, as recently shown for dupilumab-treated patients. We here asked for the role of slanMo in AD. Increased numbers of slanMo were found in AD skin lesions. In difference to other MPs in AD, slanMo lacked expression of FcɛRI, CD1a, CD14, and CD163. slanMo from blood of patients with AD expressed increased levels of CD86 and produced IL-12 and TNF-α at higher amounts than CD14+ monocytes and myeloid dendritic cells. While CD14+ monocytes from patients with AD revealed a reduced IL-12 production, we observed no difference in the cytokine production comparing slanMo in AD and healthy controls. Interestingly, experimentally induced mental stress, a common trigger of flares in patients with AD, rapidly mobilized slanMo which retained their high TNF-α-producing capacity. This study identifies slanMo as a distinct population of inflammatory cells in skin lesions and as proinflammatory blood cells in patients with AD. slanMo may, therefore, represent a potent future target for treatment of AD.
Highlights
Atopic dermatitis (AD) is the eczematous skin manifestation of atopy affecting 15–25% of children and 1–3% of adults [1]
The phenotypical analysis of sulfo LacNAc-expressing monocytes (slanMo) in lesional atopic dermatitis (AD) skin samples identified these cells as a HLA-DR+ cell population lacking expression of the Langerhans cell marker CD1a, the monocyte/Dendritic cells (DCs) marker CD14 and the macrophage marker CD163 (Figure 1C)
While IDECs are found in the epidermal and in the dermal compartment of AD skin lesions, we identify slanMo as a dermal cell population
Summary
Atopic dermatitis (AD) is the eczematous skin manifestation of atopy affecting 15–25% of children and 1–3% of adults [1]. Environmental factors such as exposure to allergens, microbial products, and psychosocial stress are relevant for disease manifestation [3, 5]. Dendritic cells (DCs), monocytes, and macrophages, collectively called mononuclear slanMo in Atopic Dermatitis phagocytes (MPs), are heterogeneous in their phenotype, function, and origin and play fundamental roles in regulating innate and adaptive immune responses in skin [6]. Unraveling the phenotypic and functional specialization of individual MP subsets within the skin compartment will enhance our understanding of how in AD pathogenic T cell responses against allergens and autoantigens as well as the quality of these responses—Th2, Th1, Th22, and Th17—are promoted and antagonized
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