1. Norepinephrine Controls Effector T Cell Differentiation through β2-Adrenergic Receptor-Mediated Inhibition of NF-κB and AP-1 in Dendritic Cells
- Author
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Alexandre S. Basso, Leandro Pires Araujo, Maisa C. Takenaka, Vanessa M. Nascimento, Marcia G. Guereschi, Rafael M. Rezende, Francisco J. Quintana, and Juliana Terzi Maricato
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,medicine.medical_specialty ,T cell ,Cellular differentiation ,Immunology ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,Biology ,Lymphocyte Activation ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Norepinephrine ,Immune system ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Receptor ,Protein kinase A ,Innate immune system ,NF-kappa B ,NF-κB ,Cell Differentiation ,Dendritic Cells ,Flow Cytometry ,Cell biology ,Mice, Inbred C57BL ,Transcription Factor AP-1 ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Female ,Receptors, Adrenergic, beta-2 ,Signal transduction ,Signal Transduction - 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 β2-adrenergic receptor (β2AR) 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 β2AR 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-κB and AP-1 signaling pathways. Moreover, as a consequence of the inverted IL-12p70/IL-23 ratio following β2AR stimulation, LPS-stimulated DC promoted the generation of CD4+ T cells that, upon TCR engagement, produced lower amounts of IFN-γ and higher levels of IL-17. These findings provide new insights into molecular and cellular mechanisms by which β2AR 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.
- Published
- 2015