Summary

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.

Overall design

An unexpected BDCA-2+CD123+CD1a+ dendritic cell (DC) subset comprised a major DC population in acute human sterile skin inflammation. Single-cell RNAseq showed these to be activated DC able to express markers normally associated with plasmacytoid DC, prompting a re-evaluation of previous studies.

Contributors

Yi-Ling Chen†, Graham Ogg✉️

Contact

graham.ogg@ndm.ox.ac.uk(Graham Ogg)