Abstract
Vagal nerve efferent activation has been shown to ameliorate the course of many inflammatory disease states. This neuro-modulatory effect has been suggested to rest on acetylcholine receptor (AChR) activation on tissue macrophages or dendritic cells (DCs). In more recent studies, vagal anti-inflammatory activity was shown involve adrenergic, splenic, pathways. Here we provide evidence that the adrenergic, rather than cholinergic, receptor activation on bone marrow derived DCs results in enhanced endocytosis uptake, enhanced IL-10 production but a decreased IL-6, IL-12p70 and IL-23 production. In antigen specific T cell stimulation assays, adrenergic β2 receptor activation on bone marrow DCs led to an enhanced potential to induce Foxp3 positive suppressive Treg cells. These effects were independent of IL10-R activation, TGFβ release, or retinoic acid (RA) secretion. Hence, adrenergic receptor β2 activation modulates DC function resulting in skewing towards anti-inflammatory T cell phenotypes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic beta-Agonists / pharmacology
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Albuterol / pharmacology
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Animals
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism
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Cells, Cultured
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Cytokines / metabolism*
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism*
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Dextrans / pharmacokinetics
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Endocytosis / drug effects
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Epinephrine / pharmacology
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Female
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Flow Cytometry
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Fluorescein-5-isothiocyanate / analogs & derivatives
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Fluorescein-5-isothiocyanate / pharmacokinetics
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Forkhead Transcription Factors / metabolism
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Inflammation Mediators / metabolism*
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Interleukin-10 / metabolism
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Interleukin-12 / metabolism
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Interleukin-23 / metabolism
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Interleukin-6 / metabolism
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Mice
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Mice, Inbred C57BL
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Receptors, Adrenergic, beta-2 / genetics
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Receptors, Adrenergic, beta-2 / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / metabolism
Substances
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Adrenergic beta-Agonists
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Cytokines
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Dextrans
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Inflammation Mediators
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Interleukin-23
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Interleukin-6
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Receptors, Adrenergic, beta-2
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fluorescein isothiocyanate dextran
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Interleukin-10
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Interleukin-12
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Fluorescein-5-isothiocyanate
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Albuterol
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Epinephrine
Grants and funding
SD, FWH and WdeJ were funded by a grant from the Dutch Organization for Scientific Research (NWO-VIDI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.