IFN-γ Contributes to the Immune Mechanisms of Hypertension
Lance Benson, Yunmeng Liu, Katherine Deck, Christoph Mora, Shengyu Mu
Abstract
Hypertension is the leading cause of cardiovascular disease and the primary risk factor for mortality worldwide. For more than half a century, researchers have demonstrated that immunity plays an important role in the development of hypertension; however, the precise mechanisms are still under investigation. The current body of knowledge indicates that proinflammatory cytokines may play an important role in contributing to immune-related pathogenesis of hypertension. Interferon gamma (IFN- γ ), in particular, as an important cytokine that modulates immune responses, has been recently identified as a critical regulator of blood pressure by several groups, including us. In this review, we focus on exploring the role of IFN- γ in contributing to the pathogenesis of hypertension, outlining the various immune producers of this cytokine and described signaling mechanisms involved. We demonstrate a key role for IFN- γ in hypertension through global knockout studies and related downstream signaling pathways that IFN- γ production from CD8 + T cell (CD8T) in the kidney promoting CD8T-stimulated salt retention via renal tubule cells, thereby exacerbating hypertension. We discuss potential activators of these T cells described by the current literature and relay a novel hypothesis for activation.