IFN- γ Contributes to the Immune Mechanisms of Hypertension

Kidney360. 2022 Oct 26;3(12):2164-2173. doi: 10.34067/KID.0001292022. eCollection 2022 Dec 29.

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.

Keywords: hypertension; immunity and inflammation; interferon-γ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Pressure / genetics
  • Blood Pressure / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cytokines
  • Humans
  • Hypertension* / genetics
  • Hypertension* / immunology
  • Interferon-gamma* / genetics
  • Interferon-gamma* / immunology

Substances

  • Cytokines
  • Interferon-gamma
  • IFNG protein, human