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Author Notes:

Corresponding author: Shengyu Mu, SMu@uams.edu

We would like to thank Dr Philip Palade (University of Arkansas for Medical Sciences, UAMS) for suggestions regarding fluorescent indicators, contribution to data discussion and editing the manuscript; Ms Shirley Haun (UAMS) for lab maintenance during the period of this work; Drs Nancy Rusch, Steven Post, Michael Jennings (UAMS) and Tatsuo Shimosawa (University of Tokyo), respectively, for comments and edits on this manuscript.

We also thank Dr David H Ellison and Ms Kayla Erspamer (Oregon Health & Science University) for kindly providing the NCC and p-NCC antibodies.

[For a full list of contributions please refer to the publication]

Subjects:

Research Funding:

This study was supported by American Heart Association Beginning Grant-in-Aid 15BGIA25730047 (S. Mu) and financial support from Dr Philip Palade and the University of Arkansas for Medical Sciences Foundation; S.W.R is supported by NIH R01 HL097107; B.K. is supported by NIDDK P30DK42086; R.S.H. is supported by VA Merit Award BX002322-01 and NIH R01-DK-085097; 3D-SIM images were acquired at the Digital Microscopy Core at UAMS supported by NIH S10 OD018065.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • SODIUM-CHLORIDE COTRANSPORTER
  • ANGIOTENSIN-II HYPERTENSION
  • SRC TYROSINE KINASE
  • BLOOD-PRESSURE
  • BARTTER-SYNDROME
  • RENAL DAMAGE
  • CHANNEL GENE
  • K CHANNEL
  • POTASSIUM
  • KIDNEY

CD8(+) T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

Tools:

Journal Title:

Nature Communications

Volume:

Volume 8

Publisher:

, Pages 14037-14037

Type of Work:

Article | Final Publisher PDF

Abstract:

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl â ' channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

Copyright information:

© The Author(s) 2017.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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