Abstract
The functions of T helper 17 (Th17) and regulatory T (Treg) cells are tightly orchestrated through independent differentiation pathways that are involved in the secretion of pro- and anti-inflammatory cytokines induced by high-salt dietary. However, the role of imbalanced Th17/Treg ratio implicated in inflammation and target organ damage remains elusive. Here, by flow cytometry analysis, we demonstrated that switching to a high-salt diet resulted in decreased Th17 cells and reciprocally increased Treg cells, leading to a decreased Th17/Treg ratio. Meanwhile, Th17-related pathway was down-regulated after one day of high salt loading, with the increase in high salt loading as shown by microarray and RT-PCR. Subsequently, blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) observed hypoxia in the renal medulla (increased R2* signal) during high-salt loading, which was regressed to its baseline level in a step-down fashion during low-salt feeding. The flow-mediated vasodilatation (FMD) of the branchial artery was significantly higher on the first day of high salt loading. Collectively, these observations indicate that a short-term increase in dietary salt intake could induce reciprocal switches in Th17/Treg ratio and related cytokines, which might be the underlying cellular mechanism of high-salt dietary induced end organ inflammation and potential atherosclerotic risk.
Highlights
A third and fourth T cell subpopulation, designated T helper 17 (Th17) and regulatory T (Treg) cells, have emerged as independent differentiation pathways[2,4,5]
Induction of pro-inflammatory Th17 cells by Serum/glucocorticoid regulated kinase 1 (SGK1) enables the activation of p38/MAPK and nuclear factor of activated T-cells 5 (NFAT5) pathways, which upregulate the expression of IL-23 receptor in a FOXO1-dependent manner and strengthen the IL-17 inflammatory cascade[2,9]
The endpoint was focused on functional dynamics of kidney and branchial artery, which were revealed by blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) and flow-mediated vasodilatation (FMD), respectively
Summary
A third and fourth T cell subpopulation, designated T helper 17 (Th17) and regulatory T (Treg) cells, have emerged as independent differentiation pathways[2,4,5]. It was demonstrated that high-salt intake could promote the development of IL-17-producing CD4+ T (Th17) cells, as an effector in response to extracellular bacterial infections and a critical mediator of autoimmune diseases[2,9]. Engagement of SGK1 activity, secondary to increased sodium chloride exposure, results in a Th1-type effector signature in Foxp3+ Tregs. This phenotype is marked by loss of suppressor function, whereas increased cellular proliferation and the secretion of cytokines[10]. The present work was designed to determine the relationship between: 1) variation in dietary salt intake and T cell subsets; 2) high dietary salt intake-induced changes in Th17/Treg-related cytokines and the inflammation of target organs. The findings might discover a pathophysiological network connecting dietary salt intake, adaptive immunity, and end organ inflammation
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