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.
<jats:p>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.</jats:p>