Neuroimmune modulation for targeting organ damage in hypertension and atherosclerosis

The brain is essential for processing and integrating sensory signals coming from peripheral tissues. Conversely, the autonomic nervous system regulated by brain centres modulates the immune responses involved in the genesis and progression of cardiovascular diseases. Understanding the pathophysiological bases of this relationship established between the brain and immune system is relevant for advancing therapies. An additional mechanism involved in the regulation of cardiovascular function is provided by the brain-mediated control of the renin-angiotensin system. In both cases, the communication is typically bidirectional and established by afferent and sensory signals collected at the level of peripheral tissues, efferent circuits, as well as of hormones. Understanding how the brain mediates the bidirectional communication and how the immune system participates in this process is object of intense investigation. This review examines key findings that support a role for these interactions in the pathogenesis of major vascular diseases that are characterized by a consistent alteration of the immune response, such as hypertension and atherosclerosis. In addition, we provide a critical appraisal of the translational implications that these discoveries have in the clinical setting where an effective management of neuroimmune and/or neuroinflammatory state might be beneficial. imagefigure legend Targeting the brain-to-spleen connection to reduce vascular damage in atherosclerosis and hypertension. The afferent and efferent arms of the circuit activated by pathological changes in atherosclerotic arteries are indicated in blue. The afferent and efferent arms of the circuit activated by hypertensive challenges are indicated in red. These circuits have two important hubs: one in the brain, where the pathological stimulus is perceived in specific areas that in turn activate peripheral autonomic efferent, and the second in the spleen, which activates egress of lymphocytes for subsequent infiltration in target organs. Created with BioRender.com. image