Norepinephrine controls effector t cell differentiation through beta 2-adrenergic receptor-mediated inhibition of nf-kappa b and ap-1 in dendritic cells

Norepinephrine controls effector t cell differentiation through beta 2-adrenergic receptor-mediated inhibition of nf-kappa b and ap-1 in dendritic cells

Author Takenaka, Maisa Carla Autor UNIFESP Google Scholar
Araujo, Leandro Pires Autor UNIFESP Google Scholar
Maricato, Juliana Terzi Autor UNIFESP Google Scholar
Nascimento, Vanessa de Mendonça Autor UNIFESP Google Scholar
Guereschi, Marcia Grando Autor UNIFESP Google Scholar
Rezende, Rafael Machado Google Scholar
Quintana, Francisco J. Google Scholar
Basso, Alexandre Salgado Autor UNIFESP Google Scholar
Abstract Despite accumulating evidence indicating that neurotransmitters released by the sympathetic nervous system can modulate the activity of innate immune cells, we still know very little about how norepinephrine impacts signaling pathways in dendritic cells (DC) and the consequence of that in DC-driven T cell differentiation. In this article, we demonstrate that beta(2)-adrenergic receptor (beta(2)AR) activation in LPS-stimulated DC does not impair their ability to promote T cell proliferation

however, it diminishes IL-12p70 secretion, leading to a shift in the IL-12p70/IL-23 ratio. Although beta(2)AR stimulation in DC induces protein kinase A-dependent cAMP-responsive element-binding protein phosphorylation, the effect of changing the profile of cytokines produced upon LPS challenge occurs in a protein kinase A-independent manner and, rather, is associated with inhibition of the NF-kappa B and AP-1 signaling pathways. Moreover, as a consequence of the inverted IL-12p70/IL-23 ratio following beta(2)AR stimulation, LPS-stimulated DC promoted the generation of CD4(+) T cells that, upon TCR engagement, produced lower amounts of IFN-gamma and higher levels of IL-17. These findings provide new insights into molecular and cellular mechanisms by which beta(2)AR stimulation in murine DC can influence the generation of adaptive immune responses and may explain some aspects of how sympathetic nervous system activity can modulate immune function.
Keywords Element-Binding Protein
Bone-Marrow
Beta(2)-Adrenergic Receptor
Cytokine Production
Molecular-Mechanisms
Innate Immunity
Kinase
Beta
Activation
Agonists
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Grant number FAPESP: 2008/58564-9
CNPq: 475000/2010-2
CNPq: 246252/2012-0
Date 2016
Published in Journal Of Immunology. Bethesda, v. 196, n. 2, p. 637-644, 2016.
ISSN 0022-1767 (Sherpa/Romeo, impact factor)
Publisher Amer Assoc Immunologists
Extent 637-644
Origin https://doi.org/10.4049/jimmunol.1501206
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000368072100020
URI http://repositorio.unifesp.br/handle/11600/49182

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