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Updated: Jul 6, 2025

Isolation and Adoptive Transfer of High Salt Treated Antigen-presenting Dendritic Cells
Published on: March 5, 2019
Dendritic cell epithelial sodium channel induced inflammation and salt-sensitive hypertension
Mert Demirci1, Antentor Hinton2, Annet Kirabo3,4,5,6
1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center.
Purpose Of Review:
Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. Epithelial sodium channel (ENaC) plays a critical role in renal electrolyte and volume regulation and has been implicated in the pathogenesis of SSBP. This review describes recent advances regarding the role of ENaC-dependent inflammation in the development of SSBP.
Recent Findings:
We recently found that sodium enters dendritic cells via ENaC, a process regulated by serum/glucocorticoid-regulated kinase 1 and epoxyeicosatrienoic acid 14,15. Sodium entry activates NADPH oxidase, leading to the production of isolevuglandins (IsoLGs). IsoLGs adduct self-proteins to form neoantigens in dendritic cells that activate T cells and result in the release of cytokines promoting sodium retention, kidney damage, and endothelial dysfunction in SSBP. Additionally, we described a novel mechanistic pathway involving ENaC and IsoLG-dependent NLRP3 inflammasome activation. These findings hold promise for the development of novel diagnostic biomarkers and therapeutic options for SSBP.
Summary:
The exact mechanisms underlying SSBP remain elusive. Recent advances in understanding the extrarenal role of ENaC have opened a new perspective, and further research efforts should focus on understanding the link between ENaC, inflammation, and SSBP.
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