A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication.
The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension.
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.|Department of Molecular Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy.
Daniela
D
Carnevale
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Marialuisa
M
Perrotta
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Fabio
F
Pallante
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Valentina
V
Fardella
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Roberta
R
Iacobucci
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Stefania
S
Fardella
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Lorenzo
L
Carnevale
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Raimondo
R
Carnevale
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Massimiliano
M
De Lucia
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.
Giuseppe
G
Cifelli
Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, 86077 Pozzilli, Italy.|Department of Molecular Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy.
Giuseppe
G
Lembo
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