Re-evaluation of human BDCA-2+ DC during acute sterile skin inflammation
Chen Y-L., Gomes T., Hardman CS., Vieira Braga FA., Gutowska-Owsiak D., Salimi M., Gray N., Duncan DA., Reynolds G., Johnson D., Salio M., Cerundolo V., Barlow JL., McKenzie ANJ., Teichmann SA., Haniffa M., Ogg G.
Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) and are traditionally defined as being BDCA-2+CD123+. pDCs are not readily detectable in healthy human skin, but have been suggested to accumulate in wounds. Here, we describe a CD1a-bearing BDCA-2+CD123int DC subset that rapidly infiltrates human skin wounds and comprises a major DC population. Using single-cell RNA sequencing, we show that these cells are largely activated DCs acquiring features compatible with lymph node homing and antigen presentation, but unexpectedly express both BDCA-2 and CD123, potentially mimicking pDCs. Furthermore, a third BDCA-2–expressing population, Axl+Siglec-6+ DCs (ASDC), was also found to infiltrate human skin during wounding. These data demonstrate early skin infiltration of a previously unrecognized CD123intBDCA-2+CD1a+ DC subset during acute sterile inflammation, and prompt a re-evaluation of previously ascribed pDC involvement in skin disease.