Next-generation vaccines may be delivered via the skin and mucosa. The stratified squamous epithelium (SSE) represents the outermost layer of the skin (epidermis) and type II mucosa (epithelium). Langerhans cells (LC) have been considered the sole antigen-presenting cells (APC) to inhabit the SSE; however, we have shown that epithelial dendritic cells (epi-DC) are also present. Importantly, epi-DC were more efficient than LCs at biding viruses.
Here we show that epi-DC are more potent at activating and polarizing T cells which makes them attractive vaccine delivery vehicles. We also show that epithelial DCs are enriched in inflamed tissues.
Using RNA sequencing we showed that SSE DCs are transcriptionally indistinguishable to DC2 in the underlaying dermis. We therefore hypothesis that SSE DCs are dermal DC2 that migrate into the SSE. Compared to their dermal counterparts, SSE DCs express higher levels of the chemokine receptors CCR5 and CXCR4 and chemokines that bind these receptors are known to meditate cell migration. We have topically applied a chemokine that binds CCR5 (CCL3/RANTES) to human trunk skin epidermis using an epidermal skin patch and shown that this does not induce migration. We will next test CXCR4 binding chemokines.
Defining the chemokine(s) responsible for driving migration of DCs into SSE is important as they could form part of vaccine delivery system to draw these cells towards vaccines which they may take up and present to T cells to drive an immune response.