TY - JOUR
T1 - Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity
AU - Chan, Camie W.
AU - Crafton, Emily
AU - Fan, Hong Ni
AU - Flook, James
AU - Yoshimura, Kiyoshi
AU - Skarica, Mario
AU - Brockstedt, Dirk
AU - Dubensky, Thomas W.
AU - Stins, Monique F.
AU - Lanier, Lewis L.
AU - Pardoll, Drew M.
AU - Housseau, Franck
N1 - Funding Information:
We thank L. Zitvogel’s group for communicating its data on IKDCs; K. Palucka and J. Banchereau for discussions. We also thank M. Delannoy for his technical assistance with electronic microscopy. We thank C. Chia and L.S. Laird for their help on the adoptive transfer experiments, and M. Jones for her technical assistance in immunofluorescence techniques. We thank F. Murillo for his technical assistance with microarray techniques. C.W.C. is supported by a Cancer Research Institute postdoctoral fellowship. This work was supported by grants from the US National Institutes of Health (NIH), the Janney Fund and Seraph Foundation, and gifts from Bill and Betty Topecer and Dorothy Needle. L.L.L. is an American Cancer Society Research Professor and is funded by NIH grants CA89189 and CA89294.
PY - 2006/3/14
Y1 - 2006/3/14
N2 - Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses1,2. We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-γ, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.
AB - Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses1,2. We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-γ, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.
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U2 - 10.1038/nm1352
DO - 10.1038/nm1352
M3 - Article
C2 - 16444266
AN - SCOPUS:32244448339
SN - 1078-8956
VL - 12
SP - 207
EP - 213
JO - Nature medicine
JF - Nature medicine
IS - 2
ER -