Immune Cells as Central Coordinators of Cardiorenal Crosstalk in Hypertension: A Narrative Review of Mechanisms, Pathways, and Therapeutic Implications

Hypertension remains the leading preventable cause of cardiovascular disease and premature death worldwide. In the hypertensive state, renal and cardiovascular dysfunctions become entrenched in a self-perpetuating feedback loop, with immune cells emerging as central coordinators of this pathological crosstalk. This narrative review examines the mechanisms by which immune cells integrate signals from high salt, the renin–angiotensin–aldosterone system (RAAS), and the sympathetic nervous system (SNS) to drive chronic inflammation and end-organ damage. We highlight the salt-dendritic cell-isolevuglandin (IsoLG)-T cell axis as a critical pathway linking dietary sodium to immune activation and hypertension. We also explore bidirectional interactions between immune cells and RAAS components, as well as neuro-immune crosstalk that amplifies sympathetic outflow. Counter-regulatory mechanisms, including the ACE2/Ang-(1-7)/Mas axis, the kallikrein–kinin system, Urodilatin, Klotho, and renalase, provide endogenous braking signals that limit inflammation. Finally, we discuss emerging immunomodulatory therapeutic strategies and identify key unanswered questions for future research. Understanding immune cells as central coordinators of cardiorenal communication offers new opportunities for precision medicine approaches to hypertension.