The nervous system and the immune system share the common ability to exert gatekeeper roles at the interfaces between internal and external environment. Although interaction between these 2 evolutionarily highly conserved systems has been recognized for long time, the investigation into the pathophysiological mechanisms underlying their crosstalk has been tackled only in recent decades. Recent work of the past years elucidated how the autonomic nervous system controls the splenic immunity recruited by hypertensive challenges. This review will focus on the neural mechanisms regulating the immune response and the role of this neuroimmune crosstalk in hypertension. In this context, the review highlights the components of the brain-spleen axis with a focus on the neuroimmune interface established in the spleen, where neural signals shape the immune response recruited to target organs of high blood pressure.