Systematic cytokine receptor profiling reveals GM-CSF as a novel TLR-independent activator of human plasmacytoid predendritic cells.
Human plasmacytoid predendritic cells (pDCs) can be activated during microbial infection through Toll-like receptor engagement. They are also involved in nonmicrobial inflammatory diseases, but their activation pathways in this context remain elusive. To identify Toll-like receptor-independent pDC activators, we performed a systematic analysis of cytokine receptors on primary human pDCs. Six receptors were expressed both at mRNA and protein levels: interleukin-3 receptor (IL-3R), IL-6R, IL-10R, IL-18R, interferon-gamma receptor, and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor. Only GM-CSF and IL-3 were able to efficiently promote pDC survival and induce their differentiation into dendritic cells. Allogeneic naive CD4 T cells primed with GM-CSF-activated pDCs produced more interferon-gamma and less IL-4 and IL-10 compared with IL-3-activated pDCs, indicating a shift in the Th1/Th2 balance. Our data point at a novel function of GM-CSF, which may serve as a link between a pathologic inflammatory environment, pDC activation, and the modulation of CD4 T-cell responses.
Ghirelli
Cristina
C
Inserm U932, Paris, France.
Zollinger
Raphaël
R
Soumelis
Vassili
V
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000235:genetics / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D017471:Receptors, Interferon; D053701:Receptors, Interleukin-10; D053724:Receptors, Interleukin-18; D016185:Receptors, Interleukin-3; D019947:Receptors, Interleukin-6; D051193:Toll-Like Receptors; D000096743:Interferon gamma Receptor