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.
authors.affiliation: Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Byung-Jin
authors.initials: BJ
authors.lastname: Kim
authors.forename: Harlan P
authors.initials: HP
authors.lastname: Jones
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000096:biosynthesis; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D004837:Epinephrine