Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity

Camie W. Chan, Emily Crafton, Hong Ni Fan, James Flook, Kiyoshi Yoshimura, Mario Skarica, Dirk Brockstedt, Thomas W. Dubensky, Monique F. Stins, Lewis L. Lanier, Drew M. Pardoll, Franck Housseau

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-213
Number of pages7
JournalNature medicine
Volume12
Issue number2
DOIs
StatePublished - Mar 14 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity'. Together they form a unique fingerprint.

  • Cite this

    Chan, C. W., Crafton, E., Fan, H. N., Flook, J., Yoshimura, K., Skarica, M., Brockstedt, D., Dubensky, T. W., Stins, M. F., Lanier, L. L., Pardoll, D. M., & Housseau, F. (2006). Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nature medicine, 12(2), 207-213. https://doi.org/10.1038/nm1352