Abstract
SummaryAngiotensin II (AngII) is a peptide hormone that affects the cardiovascular system, not only through typical effects on the vasculature, kidneys, and heart, but also through less understood roles mediated by the brain and the immune system. Here, we address the hard-wired neural connections within the autonomic nervous system that modulate splenic immunity. Chronic AngII infusion triggers burst firing of the vagus nerve celiac efferent, an effect correlated with noradrenergic activation in the spleen and T cell egress. Bioelectronic stimulation of the celiac vagus nerve, in the absence of other challenges and independently from afferent signals to the brain, evokes the noradrenergic splenic pathway to promote release of a growth factor mediating neuroimmune crosstalk, placental growth factor (PlGF), and egress of CD8 effector T cells. Our findings also indicate that the neuroimmune interface mediated by PlGF and necessary for transducing the neural signal into an effective immune response is dependent on α-adrenergic receptor signaling.
Highlights
Angiotensin II (AngII) is a peptide hormone with potent cardiovascular effects that are either induced through the cognate receptors expressed in the cardiovascular system or mediated by central actions that in turn recruit the autonomic nervous system (ANS) (Forrester et al, 2018)
Mice were implanted with osmotic minipumps containing AngII, or vehicle as control, for 3 days
3 days of AngII are enough to enhance the sympathetic nervous system (SNS) in the spleen, as evidenced by increased tyrosine hydroxylase (TH), the rate-limiting enzyme for noradrenaline synthesis, in the marginal zone marked by CD169-positive macrophages (Figure S1A, related to Figure 1)
Summary
Angiotensin II (AngII) is a peptide hormone with potent cardiovascular effects that are either induced through the cognate receptors expressed in the cardiovascular system or mediated by central actions that in turn recruit the autonomic nervous system (ANS) (Forrester et al, 2018). The immune-modulating functions of AngII are still being investigated, the splenic reservoir is known to respond to the peptide hormone. We and others have described both direct effects of AngII on the splenic immune reservoir (Cortez-Retamozo et al, 2013; Epelman et al, 2014; Swirski et al, 2009) and indirect effects mediated by central actions (Carnevale et al, 2014, 2016; Marvar et al, 2010). One efferent arm of the ANS, directed to the spleen, has been considered a critical modulator of immune responses (Bassi et al, 2020; Chavan et al, 2017; Ordovas-Montanes et al, 2015)
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