Norepinephrine Controls Effector T Cell Differentiation through beta 2-Adrenergic Receptor-Mediated Inhibition of NF-kappa B and AP-1 in Dendritic Cells

Author(s)

Takenaka, Maisa Carla ^[1] ; Araujo, Leandro Pires ^[1] ; Maricato, Juliana Terzi ^[1] ; Nascimento, Vanessa M. ^[1] ; Guereschi, Marcia Grando ^[1] ; Rezende, Rafael Machado ^[2] ; Quintana, Francisco J. ^[2] ; Basso, Alexandre S. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo - Brazil

^[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ann Romney Ctr Neurol Dis, Boston, MA 02115 - USA

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY; v. 196, n. 2, p. 637-644, JAN 15 2016.
• Web of Science Citations: 18

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. (AU)

• FAPESP's process: 08/58564-9 - Study of adaptive immune response modulation by the sympathetic nervous system: emphasis on autoimmunity, Th17 cells and Foxp3 + regulatory T cells
• Grantee: Alexandre Salgado Basso
• Support Opportunities: Research Grants - Young Investigators Grants