# Immune Cell and Epithelial Cell Interactions in Autosomal Dominant Polycystic Kidney Disease

> **NIH NIH F31** · YALE UNIVERSITY · 2023 · $47,694

## Abstract

PROJECT SUMMARY
Autosomal dominant polycystic kidney disease (ADPKD) is the most common, potentially lethal, monogenic
disease. Affecting 1:400 to 1:1000 people, mutations in PKD1 and PKD2 genes encoding polycystin-1 (PC1)
and polycystin-2, respectively, lead to development of fluid-filled cysts that progressively expand from renal
epithelial cells. This expansion damages surrounding kidney tissue, causing fibrosis, and leads to worsening
kidney function that ultimately requires dialysis or transplant. Half of the ADPKD population will experience renal
failure by the age of 50, and there are few treatment options to prevent such pathogenesis. These preventative
solutions are lacking due to limited understanding into the process of cystogenesis, meaning why cysts form and
what makes them worsen over time. Immune cells may contribute to this process. Prior literature has suggested
a role for macrophages in cyst initiation and expansion, and CD8+ T cells have recently emerged as exerting a
potential anti-cystogenic role. Using a novel transgenic suppression model of ADPKD in which a portion of the
C-terminal tail of PC1 is expressed, I will compare the immune cell populations present in a non-suppressed
disease model and the suppression model with non-cystic controls. I hypothesize that the differential immune
cell landscapes between disease models will reveal pro-cystogenic and anti-cystogenic factors that regulate
renal epithelial cells in ADPKD pathogenesis. With the expertise in ADPKD from the Caplan Lab and in
immunological investigation from the Craft Lab, I will investigate the role of immune cells in ADPKD pathogenesis
in murine models using in vivo interventional strategies, and analyze these models by flow cytometry,
immunofluorescence, and single-cell sequencing approaches. I seek to define immune cell signaling in ADPKD
and to elucidate the implications of this signaling for ADPKD pathogenesis, expecting to identify immune-
mediated factors implicated in cystogenesis. In addition to elucidating cellular signaling that modifies the cystic
and fibrotic manifestations of ADPKD, this proposal simultaneously aims to identify immune cell properties that
could serve as disease biomarkers and provide insight into treatment and monitoring strategies.

## Key facts

- **NIH application ID:** 10749617
- **Project number:** 1F31DK135356-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Victoria Rai
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749617

## Citation

> US National Institutes of Health, RePORTER application 10749617, Immune Cell and Epithelial Cell Interactions in Autosomal Dominant Polycystic Kidney Disease (1F31DK135356-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10749617. Licensed CC0.

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