Epinephrine-primed murine bone marrow-derived dendritic cells facilitate production of IL-17A and IL-4 but not IFN-γ by CD4 + T cells

Byung Jin Kim, Harlan Jones

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Sympathetic activation leading to the release of epinephrine and norepinephrine, is known as an important regulatory circuit related to immune-mediated diseases. However, questions still remain on the behavior of antigen presenting cells (APC) dictated by stress-induced sympathetic neurotransmitters. The purpose of this study was to examine the fate of bone marrow-derived dendritic cell (BMDC)-associated influences on resting CD4 + T cell activation. We hypothesize that pre-exposure of dendritic cells (DCs) can modify the intensity of cytokine production, leading to preference in resting CD4 + T cell activation. BMDCs were pre-treated with epinephrine for 2h followed by subsequent treatment of lipopolysaccharide (LPS). Subsequently, BMDCs were cocultured with purified CD4 + T cells from mouse spleen in the absence or presence of anti-CD3 stimulation in epinephrine-free media. Epinephrine pre-treatment enhanced surface expression of MHCII, CD80 and CD86. Quantitative RT-PCR showed that epinephrine pre-treatment induced a significant transcriptional decrease of IL-12p40 and a significant increase of IL-12p35 and IL-23p19. In addition, β2-adrenergic-blockade was shown to reverse these effects. Epinephrine pre-treatment also induced a significant decrease of IL-12p70 and a significant increase of IL-23 and IL-10 cytokine production. Importantly, these changes corresponded with increased IL-4 and IL-17A, but not IFN-g cytokine production by CD4 + T cells in a b2-adrenergic receptor-dependent manner. These results suggest that exposure to stress-derived epinephrine dictates dendritic cells to generate a dominant Th2/Th17 phenotype in the context of subsequent exposure to a pathogenic stimulus.

Original languageEnglish
Pages (from-to)1126-1136
Number of pages11
JournalBrain, Behavior, and Immunity
Volume24
Issue number7
DOIs
StatePublished - 1 Oct 2010

Fingerprint

Interleukin-17
Interleukin-4
Dendritic Cells
Epinephrine
Bone Marrow
T-Lymphocytes
Cytokines
Interleukin-23 Subunit p19
Interleukin-12 Subunit p35
Interleukin-12 Subunit p40
Interleukin-23
Immune System Diseases
Antigen-Presenting Cells
Interleukin-10
Adrenergic Agents
Adrenergic Receptors
Neurotransmitter Agents
Lipopolysaccharides
Norepinephrine
Spleen

Keywords

  • CD4 T cells
  • Dendritic cells
  • Epinephrine
  • Th17
  • β2-Adrenergic

Cite this

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title = "Epinephrine-primed murine bone marrow-derived dendritic cells facilitate production of IL-17A and IL-4 but not IFN-γ by CD4 + T cells",
abstract = "Sympathetic activation leading to the release of epinephrine and norepinephrine, is known as an important regulatory circuit related to immune-mediated diseases. However, questions still remain on the behavior of antigen presenting cells (APC) dictated by stress-induced sympathetic neurotransmitters. The purpose of this study was to examine the fate of bone marrow-derived dendritic cell (BMDC)-associated influences on resting CD4 + T cell activation. We hypothesize that pre-exposure of dendritic cells (DCs) can modify the intensity of cytokine production, leading to preference in resting CD4 + T cell activation. BMDCs were pre-treated with epinephrine for 2h followed by subsequent treatment of lipopolysaccharide (LPS). Subsequently, BMDCs were cocultured with purified CD4 + T cells from mouse spleen in the absence or presence of anti-CD3 stimulation in epinephrine-free media. Epinephrine pre-treatment enhanced surface expression of MHCII, CD80 and CD86. Quantitative RT-PCR showed that epinephrine pre-treatment induced a significant transcriptional decrease of IL-12p40 and a significant increase of IL-12p35 and IL-23p19. In addition, β2-adrenergic-blockade was shown to reverse these effects. Epinephrine pre-treatment also induced a significant decrease of IL-12p70 and a significant increase of IL-23 and IL-10 cytokine production. Importantly, these changes corresponded with increased IL-4 and IL-17A, but not IFN-g cytokine production by CD4 + T cells in a b2-adrenergic receptor-dependent manner. These results suggest that exposure to stress-derived epinephrine dictates dendritic cells to generate a dominant Th2/Th17 phenotype in the context of subsequent exposure to a pathogenic stimulus.",
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AU - Kim, Byung Jin

AU - Jones, Harlan

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N2 - Sympathetic activation leading to the release of epinephrine and norepinephrine, is known as an important regulatory circuit related to immune-mediated diseases. However, questions still remain on the behavior of antigen presenting cells (APC) dictated by stress-induced sympathetic neurotransmitters. The purpose of this study was to examine the fate of bone marrow-derived dendritic cell (BMDC)-associated influences on resting CD4 + T cell activation. We hypothesize that pre-exposure of dendritic cells (DCs) can modify the intensity of cytokine production, leading to preference in resting CD4 + T cell activation. BMDCs were pre-treated with epinephrine for 2h followed by subsequent treatment of lipopolysaccharide (LPS). Subsequently, BMDCs were cocultured with purified CD4 + T cells from mouse spleen in the absence or presence of anti-CD3 stimulation in epinephrine-free media. Epinephrine pre-treatment enhanced surface expression of MHCII, CD80 and CD86. Quantitative RT-PCR showed that epinephrine pre-treatment induced a significant transcriptional decrease of IL-12p40 and a significant increase of IL-12p35 and IL-23p19. In addition, β2-adrenergic-blockade was shown to reverse these effects. Epinephrine pre-treatment also induced a significant decrease of IL-12p70 and a significant increase of IL-23 and IL-10 cytokine production. Importantly, these changes corresponded with increased IL-4 and IL-17A, but not IFN-g cytokine production by CD4 + T cells in a b2-adrenergic receptor-dependent manner. These results suggest that exposure to stress-derived epinephrine dictates dendritic cells to generate a dominant Th2/Th17 phenotype in the context of subsequent exposure to a pathogenic stimulus.

AB - Sympathetic activation leading to the release of epinephrine and norepinephrine, is known as an important regulatory circuit related to immune-mediated diseases. However, questions still remain on the behavior of antigen presenting cells (APC) dictated by stress-induced sympathetic neurotransmitters. The purpose of this study was to examine the fate of bone marrow-derived dendritic cell (BMDC)-associated influences on resting CD4 + T cell activation. We hypothesize that pre-exposure of dendritic cells (DCs) can modify the intensity of cytokine production, leading to preference in resting CD4 + T cell activation. BMDCs were pre-treated with epinephrine for 2h followed by subsequent treatment of lipopolysaccharide (LPS). Subsequently, BMDCs were cocultured with purified CD4 + T cells from mouse spleen in the absence or presence of anti-CD3 stimulation in epinephrine-free media. Epinephrine pre-treatment enhanced surface expression of MHCII, CD80 and CD86. Quantitative RT-PCR showed that epinephrine pre-treatment induced a significant transcriptional decrease of IL-12p40 and a significant increase of IL-12p35 and IL-23p19. In addition, β2-adrenergic-blockade was shown to reverse these effects. Epinephrine pre-treatment also induced a significant decrease of IL-12p70 and a significant increase of IL-23 and IL-10 cytokine production. Importantly, these changes corresponded with increased IL-4 and IL-17A, but not IFN-g cytokine production by CD4 + T cells in a b2-adrenergic receptor-dependent manner. These results suggest that exposure to stress-derived epinephrine dictates dendritic cells to generate a dominant Th2/Th17 phenotype in the context of subsequent exposure to a pathogenic stimulus.

KW - CD4 T cells

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