1. A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication
- Author
-
Giuseppe Cifelli, Lorenzo Carnevale, Massimiliano De Lucia, Marialuisa Perrotta, Fabio Pallante, Valentina Fardella, Giuseppe Lembo, Stefania Fardella, Raimondo Carnevale, Roberta Iacobucci, and Daniela Carnevale
- Subjects
0301 basic medicine ,genetics and molecular biology ,T cell ,Science ,General Physics and Astronomy ,Spleen ,chemistry ,biochemistry, genetics and molecular biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,Immunity ,medicine ,biochemistry ,Receptor ,Denervation ,Multidisciplinary ,business.industry ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,030104 developmental biology ,Nicotinic agonist ,medicine.anatomical_structure ,Immunology ,Cholinergic ,business - 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., Immune system participates in the development of high blood pressure. Here the authors show that cholinergic-sympathetic pathway mediated by the α7nAChR receptor and the activation of splenic T cells prime immunity during hypertension and that selective splenic denervation protects against the onset of hypertension in mice.
- Published
- 2016