A recent study in Medical Science Monitor indicates that norepinephrine(noradrenaline), the major sympathetic nervous system neurotransmitter, through stimulation of β2-adrenoceptors (AR) is able to suppress the highly pathogenic T helper 17 (Th17) cells and exert anti-inflammatory effects in a mouse model of arthritis.
In the Medical Science Monitor study, Yan Liu and colleagues from the Nantong University, Nantong, Jiangsu, China investigated the expression of β2-AR by CD4+ T cells and the effects of norepinephrine on the Th17 cell differentiation and function in the mouse CIA model of rheumatoid arthritis.
The researchers found that CD4+ T cells expressed β2-AR, and the expression was downregulated during the CIA disease progression. It is known that naive CD4+ T cells and effector Th1 (but not Th2) cells express β2-ARs. Here, Liu et al. provide evidence that β2-ARs are also expressed on Th17 cells, and that this expression is reduced by the CIA condition.
While, the CIA disease model induced an increase of IL-17 and IL-22 production, CD25–IL-17+ cell percentage, and the ROR-γt expression in CD4+ T cells, norepinephrine reduced the T cell shift towards Th17 phenotype and a β2-ARs antagonist reversed this effect.
Importantly, the β2-AR agonist terbutaline inhibited the CIA-induced IL-17 and IL-22 expression, and the expression of the Th17 cell-specific transcriptional factor ROR-γt. Terbutaline also reduced the CIA-induced CD4+ T cell proliferation and the shift towards Th17 phenotype though a protein kinase A (PKA)-dependant pathway.
Overall, these results indicate that the sympathetic nervous system neuromediator norepinephrine, though activation of the β2-AR/PKA pathway is able to down-regulate the development and activity of Th17 cells, and thus, in turn to exert anti-inflammatory effects in the mouse CIA arthritis model.
This may also suggest that β2-adrenoceptor agonists hold a theurapeutic potential in rheumatoid arthritis.
Source: Med Sci Monit, 2018, 24:1196-1204. Read More: Med Sci Monit
Cover image credit (right panel): Norepinephrine (labeled “noradrénaline” in this drawing) processing in a synapse. After release norepinephrine can either be taken up again by the presynaptic terminal, or broken down by enzymes; synapse noradrénergique; Wikipedia, By Pancrat – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15190181