# Investigating CD4 T regulatory cells during rapid cystogenesis

> **NIH NIH K01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $153,165

## Abstract

Project Abstract
Cystic kidney diseases affect 1:500 people and account for 5-10% of all patients with end stage renal disease
representing a significant health care burden. This spectrum of disorders is caused by mutations in proteins
required for cilia formation (Intraflagellar transport protein 88, Ift88) or function (Polycystin 1, Pkd1; Polycsytin 2,
Pkd2). In addition, patients with these disorders experience periods of slow focal cyst formation and rapid, severe
cyst progression. Data from mouse models indicate that loss of cilia related proteins (Ift88, Pkd1, Pkd2) results
in slow focal cyst formation suggesting that additional environmental factors are required for rapid cystogenesis
often observed in human patients. This hypothesis is supported by data from multiple labs, including our own,
indicating that renal injury promotes rapid cystogenesis in mice with cilia dysfunction. Importantly, renal injury
promotes the accumulation of immune cells in wild type mice. Data from our lab and others indicate that immune
cell accumulation is further enhanced and prolonged in mice with cilia dysfunction suggesting that persistent
immune cell accumulation may be the cause of rapid cyst formation following injury in mice with cilia dysfunction.
However, the type of immune cell that promotes cystic disease following injury is poorly understood and
represents a gap in knowledge. The preliminary data outlined in this application show that genetic deletion of all
adaptive immune cells (CD4 T cells, CD8 T cells, and B cells) or pharmacological depletion of just CD4 T cells
reduces cyst severity following injury in mice with cilia dysfunction suggesting that CD4 T cells may be the critical
link between renal injury and rapid cystogenesis. To identify the subtype of CD4 T cell important in this process,
we performed flow cytometry analysis of control and cilia mutant kidneys at various time points following injury.
Our preliminary data indicate that mice with cilia dysfunction have increased and persistent accumulation of
CD4+ Foxp3+ T regulatory cells (Tregs). These data led to the overall hypothesis that increased and
persistent accumulation of Tregs following injury causes prolonged and abnormal epithelial proliferation
and rapid cyst expansion in mice with cilia dysfunction. The goal of this application is to identify the
mechanistic link between rapid cystogenesis and T regulatory cells. Our hypotheses will be tested with the
following specific aims: 1. To test the hypothesis that cilia dysfunction causes persistent and/or enhanced
accumulation of Tregs in regions adjacent to expanding cysts following renal injury. 2. To test the hypothesis
that Tregs promote injury induced cyst expansion in conditional Ift88 mice through secretion of IL-10, a cytokine
that is predominantly produced by Tregs and has previously been reported to drive cystic epithelial cell
proliferation. Data collected from this proposal will be used to develop novel immune cell modula...

## Key facts

- **NIH application ID:** 9891171
- **Project number:** 1K01DK119375-01A1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Kurt A Zimmerman
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,165
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891171

## Citation

> US National Institutes of Health, RePORTER application 9891171, Investigating CD4 T regulatory cells during rapid cystogenesis (1K01DK119375-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891171. Licensed CC0.

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