Re-evaluation of human BDCA-2+ DC during acute sterile skin inflammation

J Exp Med. 2020 Mar 2;217(3):jem.20190811. doi: 10.1084/jem.20190811.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / physiology
  • Antigens, CD1 / metabolism
  • Dendritic Cells / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Interleukin-3 Receptor alpha Subunit / metabolism
  • Lectins, C-Type / metabolism*
  • Lymph Nodes / metabolism
  • Membrane Glycoproteins / metabolism*
  • Receptors, Immunologic / metabolism*
  • Skin / metabolism*

Substances

  • Antigens, CD1
  • CD1a antigen
  • CLEC4C protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Receptors, Immunologic