Critics role of IL-21 and T follicular helper cells in hypertension and vascular dysfunction


Dale B. L., Pandey A. K., Chen Y., Smart C. D., Laroumanie F., Ao M., ...More

JCI INSIGHT, vol.4, no.11, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 4 Issue: 11
  • Publication Date: 2019
  • Doi Number: 10.1172/jci.insight.129278
  • Journal Name: JCI INSIGHT
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED)
  • Dokuz Eylül University Affiliated: No

Abstract

T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce IL-21 promote germinal center (GC) B cell responses, leading to lg production. Here we investigate the role of IL-21 and Tfh cells in hypertension. In response to angiotensin II-induced (Ang II-induced) hypertension, T cell IL-21 production was increased, and Il21(-/-) mice developed blunted hypertension, attenuated vascular end-organ damage, and decreased IL-17A and IFN-gamma production. Tfh-like cells and GC B cells accumulated in the aorta, and plasma IgG1 was increased in hypertensive WT but not or Il21(-/-) mice. Furthermore, Tfh cell-deficient mice developed blunted hypertension and vascular hypertrophy in response to Ang II infusion. Importantly, IL-21 neutralization reduced BP and reversed endothelial dysfunction and vascular inflammation. Moreover, recombinant IL-21 impaired endothelium-dependent relaxation ex vivo and decreased NO production from cultured endothelial cells. Finally, we show in humans that peripheral blood T cell production of IL-21 correlated with systolic BP and IL-17A production. These data suggest that IL-21 may be a novel therapeutic target for the treatment of hypertension and its micro- and macrovascular complications.