Systematic cytokine receptor profiling reveals GM-CSF as a novel TLR-independent activator of human plasmacytoid predendritic cells

Blood. 2010 Jun 17;115(24):5037-40. doi: 10.1182/blood-2010-01-266932. Epub 2010 Apr 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology*
  • Gene Expression Profiling
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interferon gamma Receptor
  • RNA, Messenger / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism
  • Receptors, Interleukin-10 / genetics
  • Receptors, Interleukin-10 / metabolism
  • Receptors, Interleukin-18 / genetics
  • Receptors, Interleukin-18 / metabolism
  • Receptors, Interleukin-3 / genetics
  • Receptors, Interleukin-3 / metabolism
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / metabolism
  • Toll-Like Receptors / metabolism*

Substances

  • RNA, Messenger
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptors, Interferon
  • Receptors, Interleukin-10
  • Receptors, Interleukin-18
  • Receptors, Interleukin-3
  • Receptors, Interleukin-6
  • Toll-Like Receptors
  • Granulocyte-Macrophage Colony-Stimulating Factor