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.
Re-evaluation of human BDCA-2+ DC during acute sterile skin inflammation
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Yi-Ling Chen, Tomas Gomes, Clare S. Hardman, Felipe A. Vieira Braga, Danuta Gutowska-Owsiak, Maryam Salimi, Nicki Gray, David A. Duncan, Gary Reynolds, David Johnson, Mariolina Salio, Vincenzo Cerundolo, Jillian L. Barlow, Andrew N.J. McKenzie, Sarah A. Teichmann, Muzlifah Haniffa, Graham Ogg; Re-evaluation of human BDCA-2+ DC during acute sterile skin inflammation. J Exp Med 2 March 2020; 217 (3): e20190811. doi: https://doi.org/10.1084/jem.20190811
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