# Deep phenotypic and functional characterization of salt-responsive immune cells in human salt senstive hypertension using CTE-seq

> **NIH NIH R03** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $86,500

## Abstract

Project Summary:
Salt-sensitive hypertension is an independent predictor of death due to cardiovascular disease
(CVD), but the mechanisms are poorly understood. Most of the research on salt-sensing
mechanisms has focused on the kidney, the vasculature and the brain; however, recent studies
from our laboratory have found that immune cells including antigen presenting cells (APCs) can
sense sodium (Na+) and contribute to salt-induced hypertension and end organ damage through
a mechanism involving increased lipid oxidation and formation of immunogenic gamma
ketoaldehydes known as isolevuglandins (IsoLGs) or isoketals. Emerging evidence suggests that
Na+ accumulates in the interstitium and activates immune cells but the specific tissue location
including the origin, antigenic site, and final target for salt-activated immune cell in cardiovascular
tissues is not known. Tools to study T cells have been rapidly expanding over the past 5 years
along with increased computing capacity including single T cells sequencing of α and β chain T
cell receptor spectra typing but very few studies have investigated APCs using these advanced
techniques and we do not know where or how they are activated and in turn activate T cells in
salt-induced CVD. We propose an innovative approach to use 5’ CITE-Seq and post hoc
sequencing, to phenotype APCs in people with salt-sensitivity of blood pressure. We will couple
the immune phenotype with IsoLG formation using our innovative approach to conjugate the anti-
IsoLG D11 ScFv antibody sequence with an oligo and use CITE-Seq to track these important
activated IsoLG-positive cells and determine if these are associated with gene expression of
sodium channels. Identifying the immune cells associated with salt-sensitivity of blood pressure
will have a far-ranging impact on our understanding of the pathogenesis of salt-induced
hypertension and other diseases aggravated by high salt consumption.

## Key facts

- **NIH application ID:** 10095170
- **Project number:** 1R03HL155041-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Annet Kirabo Kirabo
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $86,500
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10095170

## Citation

> US National Institutes of Health, RePORTER application 10095170, Deep phenotypic and functional characterization of salt-responsive immune cells in human salt senstive hypertension using CTE-seq (1R03HL155041-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10095170. Licensed CC0.

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