Understanding the Spatial Relationship Between Dendritic Cells and Tight Junctions in the Human Epidermis

Although disruption of epidermal tight junctions (TJs) is thought to promote immunological responses to epicutaneous antigens or allergens, the physical relationship between TJs and skin resident dendritic cells is still poorly understood. We stain whole-mount human epidermis to investigate the spatial relationship between TJs structure and antigen presenting cells, including dendritic cells (DCs) and the main epidermal dendritic cells called Langerhans cells (LCs).  We are interested in understanding whether the appearance of these structures/cells differ between patients with atopic dermatitis or healthy individuals.

Our preliminary image analysis of TJs and LCs, identified notable differences between nonlesional AD epidermis and epidermis from healthy individuals. We observed increased numbers of DCs and LCs in the epidermis from AD subjects. We also found that AD nonlesional skin more commonly has a distorted TJ architecture that we have termed “fragmented” based on the occludin staining pattern. This altered TJ structure is spatially associated with a greater number and the notable clustering of activated LCs. These findings suggest that alterations we observed in LCs in close proximity to the “fragmented” TJ epidermal areas, which is more commonly seen in AD samples, suggest that there is a dynamic crosstalk between epidermal barrier and antigen presenting cells.

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