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.

A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication / Carnevale, Daniela; Perrotta, Marialuisa; Pallante, Fabio; Fardella, Valentina; Iacobucci, Roberta; Fardella, Stefania; Carnevale, Lorenzo; Carnevale, Raimondo; De Lucia, Massimiliano; Cifelli, Giuseppe; Lembo, Giuseppe. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 7:(2016). [10.1038/ncomms13035]

A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

CARNEVALE, DANIELA
;
Perrotta, Marialuisa;Cifelli, Giuseppe;LEMBO, Giuseppe
2016

Abstract

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.
2016
chemistry; biochemistry, genetics and molecular biology
01 Pubblicazione su rivista::01a Articolo in rivista
A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication / Carnevale, Daniela; Perrotta, Marialuisa; Pallante, Fabio; Fardella, Valentina; Iacobucci, Roberta; Fardella, Stefania; Carnevale, Lorenzo; Carnevale, Raimondo; De Lucia, Massimiliano; Cifelli, Giuseppe; Lembo, Giuseppe. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 7:(2016). [10.1038/ncomms13035]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/952542
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