Specialization, kinetics, and repertoire of type 1 interferon responses by human plasmacytoid predendritic cells.
Recent studies suggest plasmacytoid predendritic cells (pDCs) and myeloid dendritic cells (mDCs) have the functional plasticity to produce similar amounts of type 1 interferons (IFNs) and interleukin-12 (IL-12), challenging the concept and existence of DC subsets with distinct function. In this study, we demonstrate that previous studies showed human pDCs produce large amounts of IL-12 because of contaminating mDCs. Using highly purified human DC subsets, we found that although pDCs make 300 times more IFN-alpha than mDCs and mDCs make 13 times more IL-12 p70 than pDCs in response to all the toll-like receptor ligands and CD40 ligands, pDCs rapidly make large amounts of IFN-alpha within the first 12 hours of activation and become refractory to further stimulation. pDCs preferentially expressed the transcriptional factors critical for type 1 IFN, but not for IL-12 transcription, and they dedicated 60% of new transcriptional activity to make 19 type 1 IFN subtypes. This study provides formal proof that the plasticity of DC subsets is limited and that different DC subsets evolve to perform distinct functions in linking innate and adaptive immunity.
Ito
Tomoki
T
Department of Immunology and Center for Cancer Immunology Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-1903, USA.
Kanzler
Holger
H
Duramad
Omar
O
Cao
Wei
W
Liu
Yong-Jun
YJ
D023201:CD40 Ligand; D002469:Cell Separation / Q000379:methods / Q000592:standards; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007370:Interferon Type I / Q000096:biosynthesis*; D016898:Interferon-alpha / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007700:Kinetics; D008024:Ligands; D051193:Toll-Like Receptors; D014158:Transcription, Genetic
D007370:Interferon Type I; D016898:Interferon-alpha; D008024:Ligands; D051193:Toll-Like Receptors; D023201:CD40 Ligand; D018664:Interleukin-12