| First Author | Takenaka MC | Year | 2016 |
| Journal | J Immunol | Volume | 196 |
| Issue | 2 | Pages | 637-44 |
| PubMed ID | 26663782 | Mgi Jnum | J:254001 |
| Mgi Id | MGI:6101556 | Doi | 10.4049/jimmunol.1501206 |
| Citation | Takenaka MC, et al. (2016) Norepinephrine Controls Effector T Cell Differentiation through beta2-Adrenergic Receptor-Mediated Inhibition of NF-kappaB and AP-1 in Dendritic Cells. J Immunol 196(2):637-44 |
| abstractText | 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 beta2-adrenergic receptor (beta2AR) 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 beta2AR 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-kappaB and AP-1 signaling pathways. Moreover, as a consequence of the inverted IL-12p70/IL-23 ratio following beta2AR 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 beta2AR 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. |
