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Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury
Purvi Mehrotra, Michael Sturek, Javier A. Neyra, and David P. Basile
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First published February 3, 2020 - More info
J Clin Invest. 2020;130(2):1052–1052. https://doi.org/10.1172/JCI135716.
© 2020 American Society for Clinical Investigation
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Abstract
We hypothesized that the store-operated calcium entry (SOCE) channel, Orai1, participates in the activation of Th17 cells and influences renal injury. In rats, following renal ischemia/reperfusion (I/R), there was a rapid and sustained influx of Orai1+ CD4 T cells and IL-17 expression was restricted to Orai1+ cells. When kidney CD4+ cells of post–acute kidney injury (post-AKI) rats were stimulated with angiotensin II and elevated Na+ (10–7 M/170 mM) in vitro, there was an enhanced response in intracellular Ca2+ and IL-17 expression, which was blocked by SOCE inhibitors 2APB, YM58483/BTP2, or AnCoA4. In vivo, YM58483/BTP2 (1 mg/kg) attenuated IL-17+ cell activation, inflammation, and severity of AKI following either I/R or intramuscular glycerol injection. Rats treated with high-salt diet (5–9 weeks after I/R) manifested progressive disease indicated by enhanced inflammation, fibrosis, and impaired renal function. These responses were significantly attenuated by YM58483/BTP2. In peripheral blood of critically ill patients, Orai1+ cells were significantly elevated by approximately 10-fold and Th17 cells were elevated by approximately 4-fold in AKI versus non-AKI patients. Further, in vitro stimulation of CD4+ cells from AKI patients increased IL-17, which was blocked by SOCE inhibitors. These data suggest that Orai1 SOCE is a potential therapeutic target in AKI and CKD progression.
Authors
Purvi Mehrotra, Michael Sturek, Javier A. Neyra, David P. Basile
Original citation: J Clin Invest. 2019;129(11):4951–4961. https://doi.org/10.1172/JCI126108
Citation for this corrigendum: J Clin Invest. 2020;130(2):1052. https://doi.org/10.1172/JCI135716
Following the publication of this article, a reader noted that Figure 4I and Supplemental Figure 1 contained images that were previously published in a Kidney International publication by the same group (1). The authors have indicated that the errors in Figure 4I occurred during figure preparation and have provided the corrected panel below. In addition, the authors have provided an updated version of Supplemental Figure 1 to illustrate the gating strategy used in the study in this article. The online version of the supplemental data has been updated to reflect this change.
The authors regret the error.
Copyright © 2020 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)