Journal Article

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

Liu, Yunmeng, Ko, Benjamin, Hoover, Robert S., Rafferty, Tonya M., Mu, Shengyu, Rhee, Sung W., Song, Li, He, Beixiang, Webber, Jessica S.

2017

Overview

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 − 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. T cells contribute to development of high blood pressure but their role in salt-sensitive hypertension is less clear. Liu et al . show that CD8 + T cells upregulate and activate Na-Cl co-transporter NCC in distal convoluted tubules via direct cell-cell contact and ROS-Src activation, leading to Na + retention and salt-sensitive hypertension.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 14 / 14/63 / 631/250/2152 / 631/443/272 / 64 / 692/699/75/243/785 / 82 / 96 / Adoptive Transfer / Animals / Blood pressure / CD8-Positive T-Lymphocytes - drug effects / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - pathology / CD8-Positive T-Lymphocytes - transplantation / Chloride / Chloride Channels - genetics / Chloride Channels - immunology / Chlorides - immunology / Chlorides - metabolism / Coculture Techniques / Deoxycholic Acid - administration & dosage / Epithelial Cells - drug effects / Epithelial Cells - immunology / Epithelial Cells - pathology / Gene Expression Regulation / Humanities and Social Sciences / Hypertension / Hypertension - chemically induced / Hypertension - genetics / Hypertension - immunology / Hypertension - pathology / Ion Transport / Kidney Tubules, Distal - drug effects / Kidney Tubules, Distal - immunology / Kidney Tubules, Distal - pathology / Kidneys / Kinases / Lymphocytes / Male / Mice / Mice, Inbred C57BL / multidisciplinary / Mutation / Neurosciences / Pathogenesis / Potassium / Potassium Channels, Inwardly Rectifying - genetics / Potassium Channels, Inwardly Rectifying - immunology / Rats / Reactive Oxygen Species - immunology / Reactive Oxygen Species - metabolism / Retention / Salt / Salts / Science / Science (multidisciplinary) / Signal Transduction / Sodium / Sodium - immunology / Sodium - metabolism / Solute Carrier Family 12, Member 3 - genetics / Solute Carrier Family 12, Member 3 - immunology / src-Family Kinases - genetics / src-Family Kinases - immunology