PVAT-conditioned media from Dahl S rats on high fat diet promotes inflammatory cytokine secretion by activated T cells prior to the development of hypertension

Abstract

There is considerable evidence that the immune system plays a role in hypertension, however this role is not fully characterized. Our previous studies demonstrated that mesenteric perivascular adipose tissue (mPVAT) harbors a large T cell population, which is a cell type identified as contributing to hypertension. In the present study, we tested the hypothesis that soluble mediators in mPVAT influence T cell function just prior to the development of hypertension. Toward this end, we utilized a unique model of hypertension in which Dahl S rats on a high fat (HF) diet develop hypertension. We found that conditioned media (CM) from mPVAT from healthy Dahl S rats on control diet buffers T cell activation, however, mPVATCM from Dahl S rats on a HF diet markedly increased inflammatory cytokine induction (IFNγ, GM-CSF and IL-17a) by activated T cells. These cytokines are known to promote activation of macrophages and neutrophils, among other effects. Conversely, the antiinflammatory cytokine, IL-10, was not different between the groups, suggesting the effect is selective for inflammatory cytokines. Furthermore, we conducted bulk RNA-seq on activated T cells cultured in mPVAT-CM from Dahl S rats on either control (CTL) or HF diet for 10 weeks. In accordance with the cytokine analysis, mPVAT-CM from HF diet-fed rats significantly upregulated many genes associated with IFNγ/IL-17 induction, whereas Th2/ Treg-associated genes were downregulated. Taken together, these data strongly suggest soluble mediators from mPVAT influence T cell inflammatory status and may promote Th1/ Th17 differentiation preceding the development of hypertension triggered by HF diet.