The Influence of Interleukin 21 and T Follicular Helper Cells in Hypertension and Vascular Dysfunction

Abstract

The role of T and B cells of the adaptive immune have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce interleukin 21 (IL- 21), can act upstream of IL-17A and interferon gamma (IFNg) which are known to promote hypertension, as well as promote germinal center (GC) B cell responses leading to immunoglobulin (Ig) production. The role of IL-21 and Tfh cells were investigated using two mouse models, Il21-/- mice, and Bcl6flox/floxTgCD4cre mice, as well as pharmacological intervention after the onset of hypertension using therapeutic grade neutralizing antibodies to murine IL-21. The impact genetic mouse lines or therapeutic intervention had on hypertension and end-organ damage were assessed by blood pressure measurements, vascular reactivity studies, vascular inflammation, and aortic remodeling. The results of these studies were associated with hypertension in humans through measurement of T cell production of IL-21 and IL-17A from peripheral blood. Additionally, through the use of mass cytometry and cytometry by time of flight (CyTOF), the ability to identify and detect previously unknown producing cells of IL-17A and INFg was accomplished.