Heterogeneity within tissue-specific macrophage and dendritic cell populations during cutaneous inflammation in atopic dermatitis

Background Macrophages and dendritic cells may play a role in chronicity of atopic dermatitis (AD); however, so far only limited data are documented on the distribution of these cells in the skin during cutaneous inflammation. Objectives To gain better insight into the presence and distribution of macrophage and dendritic cell (sub)populations in acutely and chronically inflamed skin of AD patients. Methods Chronic inflammatory reactions were studied in lesional AD skin biopsies; the atopy patch test was used as a model for the initiation of AD lesions, representing acute inflammation. To determine the number and phenotype of different dermal macrophage and dendritic cell populations immunohistochemistry and digital imaging were used. Results There was an increase in macrophage numbers in acutely and chronically inflamed AD skin, whereas absolute dendritic cell numbers were unchanged, compared with non-lesional AD skin. Furthermore, phenotypically heterogeneous and overlapping macrophage and dendritic cell populations were present in inflamed AD skin. The classic macrophage marker CD68 and prototypic dendritic cell marker CD1a could bind to the same cell subpopulation in the dermis of inflamed AD skin. Mannose receptors were expressed mainly by macrophages in inflamed AD skin. Conclusions In this study we observed changes in macrophage number and phenotype during cutaneous inflammation in AD. Dendritic cell numbers did not change: however, phenotypically dendritic cell and macrophage subpopulations showed increasing overlap during inflammation in AD skin. We show for the first time that within tissue-specific macrophage populations further subpopulations are present, and that monocyte-derived cells may express markers for both dendritic cells and macrophages. Our results point to the existence of a heterogeneous pool of macrophage/dendritic cell-like cells, from which subpopulations of dermal macrophages and dendritic cells arise.