# T cell Trafficking in Uremic Cardiomyopathy

> **NIH NIH R03** · EMORY UNIVERSITY · 2021 · $37,674

## Abstract

ABSTRACT
 Chronic kidney disease (CKD) confers increased risk for cardiovascular disease. Uremic cardiomyopathy,
characterized by left ventricular hypertrophy and diastolic dysfunction is a leading cardiovascular complication
of CKD. Targeting traditional CVD risk factors has not significantly improved outcomes in the CKD population,
underscoring the need for improved understanding and identification of early risk factors amenable to
treatment in the CKD population. Rigorous studies in animal models now support a role for CD4+ T cells in the
pathogenesis of heart failure induced by pressure overload and now CKD. This R03 proposal will enhance the
activities of the K08-funded PI as they pursue independent funding to further understand the mechanistic role
of T cell infiltration in the development of cardiac dysfunction during CKD.
 The R03 project has two Aims: 1) to determine the role of the CXCR3 pathway in the recruitment of T cells
into the heart during CKD, and 2) to determine the functional capacity of heart-infiltrating T cells during CKD. In
Aim 1, we will first define the temporal course of chemokine production, including the relative expression and
cellular sources of CXCR3 ligands, in relation to T cell infiltration early following CKD-induction. Next, we will
determine the necessity of CXCR3 in the early recruitment of T cells during CKD by complementary
approaches of pharmacological blockade or knockdown of leukocyte expression of CXCR3. Finally, we will
determine whether constitutive expression of CXCR3 by T cells is sufficient for their infiltration into the heart
during CKD. In Aim 2, we will define the CD4+ helper T cell subsets infiltrating the heart during CKD in the
presence and absence of CXCR3 blockade. Finally, we will determine whether T cell infiltration into the uremic
heart is antigen specific by assessing the ability of transgenic T cells that recognize a foreign antigen
(ovalbumin, OT-II) to infiltrate the hearts and become activated during CKD. Results from the outlined
experiments will provide preliminary data, as well as experience in techniques for the genetic modification of T
cells, to support the K08 awardee's application for an R01 proposal to evaluate the impact of T cell trafficking
pathways on the development of cardiac dysfunction in CKD.

## Key facts

- **NIH application ID:** 10129083
- **Project number:** 1R03DK124736-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Pamela D Winterberg
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,674
- **Award type:** 1
- **Project period:** 2021-08-01 → 2022-04-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129083

## Citation

> US National Institutes of Health, RePORTER application 10129083, T cell Trafficking in Uremic Cardiomyopathy (1R03DK124736-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129083. Licensed CC0.

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