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

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^- 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5227995 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA significant mechanism of salt-tolerance in rice is the ability to remove Na+ and Cl- in the leaf sheath, which limits the entry of these toxic ions into the leaf blade. The leaf sheath removes Na+ mainly in the basal parts, and Cl- mainly in the apical parts. These ions are unloaded from the xylem vessels in the peripheral part and sequestered into the fundamental parenchyma cells at the central part of the leaf sheath.ResultsThis study aimed to identify associated Na+ and Cl- transporter genes with this salt removal ability in the leaf sheath of rice variety FL 478. From 21 known candidate Na+ and Cl- transporter rice genes, we determined the salt responsiveness of the expression of these genes in the basal and apical parts, where Na+ or Cl- ions were highly accumulated under salinity. We also compared the expression levels of these transporter genes between the peripheral and central parts of leaf sheaths. The expression of 8 Na+ transporter genes and 3 Cl- transporter genes was up-regulated in the basal and apical parts of leaf sheaths under salinity. Within these genes, OsHKT1;5 and OsSLAH1 were expressed highly in the peripheral part, indicating the involvement of these genes in Na+ and Cl- unloading from xylem vessels. OsNHX2, OsNHX3, OsNPF2.4 were expressed highly in the central part, which suggests that these genes may function in sequestration of Na+ and Cl- in fundamental parenchyma cells in the central part of leaf sheaths under salinity. Furthermore, high expression levels of 4 candidate genes under salinity were associated with the genotypic variation of salt removal ability in the leaf sheath.ConclusionsThese results indicate that the salt removal ability in rice leaf sheath may be regulated by expressing various Na+ or Cl- transporter genes tissue-specifically in peripheral and central parts. Moreover, some genes were identified as candidates whose expression levels were associated with the genotypic variation of salt removal ability in the leaf sheath. These findings will enhance the understanding of the molecular mechanism of salt removal ability in rice leaf sheath, which is useful for breeding salt-tolerant rice varieties.

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

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OmicsDI is part of the ELIXIR infrastructure

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

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OmicsDI is part of the ELIXIR infrastructure

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