Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons.
Plasmacytoid dendritic cells (pDCs) are specialized type I interferon (IFN-α/β)-producing cells that express intracellular toll-like receptor (TLR) 7 and TLR9 and recognize viral nucleic acids in the context of infections. We show that pDCs also have the ability to sense host-derived nucleic acids released in common skin wounds. pDCs were found to rapidly infiltrate both murine and human skin wounds and to transiently produce type I IFNs via TLR7- and TLR9-dependent recognition of nucleic acids. This process was critical for the induction of early inflammatory responses and reepithelization of injured skin. Cathelicidin peptides, which facilitate immune recognition of released nucleic acids by promoting their access to intracellular TLR compartments, were rapidly induced in skin wounds and were sufficient but not necessary to stimulate pDC activation and type I IFN production. These data uncover a new role of pDCs in sensing tissue damage and promoting wound repair at skin surfaces.
Department of Immunology, the University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Josh
J
Gregorio
Stephan
S
Meller
Curdin
C
Conrad
Anna
A
Di Nardo
Bernhard
B
Homey
Antti
A
Lauerma
Naoko
N
Arai
Richard L
RL
Gallo
John
J
Digiovanni
Michel
M
Gilliet
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000172:deficiency / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D009696:Nucleic Acids / Q000276:immunology / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000293:injuries; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000235:genetics; D014945:Wound Healing / Q000276:immunology*
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D007370:Interferon Type I; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009696:Nucleic Acids; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D053633:Receptor, Interferon alpha-beta