Th-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism.

TitleTh-17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT-1R antagonism.
Publication TypeJournal Article
Year of Publication2015
JournalKidney international
Volume88
Issue4
Pagination776-84
ISSN0085-2538
Abstract

Exposure of rats to elevated dietary salt following recovery from acute kidney injury (AKI) accelerates the transition to chronic kidney disease (CKD), and is dependent on lymphocyte activity. Here we tested whether high salt diet triggers lymphocyte activation in postischemic kidneys to worsen renal inflammation and fibrosis. Male Sprague-Dawley rats on a 0.4% salt diet were subjected to left unilateral ischemia-reperfusion and allowed to recover for 5 weeks. This resulted in a mild elevation of CD4(+) T cells relative to sham animals. Contralateral unilateral nephrectomy and elevated dietary salt (4%) for 4 extra weeks hastened CKD and interstitial fibrosis. Activated T cells were increased in the kidney threefold after 4 weeks of elevated dietary salt exposure relative to post-AKI rats before salt feeding. The T cell subset was largely positive for IL-17, indicative of Th-17 cells. Because angiotensin II activity may influence lymphocyte activation, injured rats were given the AT1R antagonist, losartan, along with high salt diet. This significantly reduced the number of renal Th-17 cells to levels of sham rats, and significantly reduced the salt-induced increase in fibrosis to about half. In vitro studies in AKI-primed CD4(+) T cells indicated that angiotensin II and extracellular sodium enhanced, and losartan inhibited, IL-17 expression. Thus, dietary salt modulates immune cell activity in postischemic recovering kidneys because of the activity of local RAS, suggesting the participation of these cells in CKD progression post-AKI.

URLhttps://linkinghub.elsevier.com/retrieve/pii/S2157-1716(15)32262-0
DOI10.1038/ki.2015.200
Short TitleKidney Int
X
Enter your linkblue username.
Enter your linkblue password.
Secure Login

This login is SSL protected

Loading