# Role of regulatory T cells in adverse pregnancy outcomes after ischemia reperfusion injury

> **NIH NIH K99** · AUGUSTA UNIVERSITY · 2021 · $110,938

## Abstract

PROJECT ABSTRACT
Role of regulatory T cells in adverse pregnancy outcomes after ischemia reperfusion injury
Acute kidney injury (AKI) is increasingly prevalent worldwide, affecting an estimated 1 in 5 adults under
hospital care. Recovery mechanisms from AKI, are not fully understood, and current markers for AKI
recovery, including serum creatinine, may misrepresent recovery status. There is increasing evidence
that AKI patients have lingering subclinical injury after AKI, despite serum creatinine values returning to
normal, as AKI patients have higher mortality rates than patients without AKI. A recent clinical study
reported that women with a history of AKI have poor maternal and fetal outcomes during pregnancy,
suggesting that subclinical injury after AKI leaves these patients unable to cope with the increased
renal demands of pregnancy. The goal of this proposal is to address the critical gap in knowledge
regarding the mechanisms by which AKI predisposes females to adverse pregnancy outcomes using
ischemia reperfusion (IR) injury as an experimental animal model of AKI. In the current studies, we
propose that regulatory T cells (Tregs) act as a critical link between AKI and poor pregnancy outcomes.
Our central hypothesis is that subclinical injury after IR inhibits expansion of Tregs during pregnancy,
which limits nitric oxide bioavailability and results in poor maternal and fetal outcomes. Our hypothesis
is supported by strong preliminary data showing that despite allowing 1 month of recovery following IR
and return of plasma creatinine to basleline values, female Sprague Dawley rats have significantly
smaller pups and higher rates of fetal demise compared to time-control rats that received sham
surgery. Furthermore, Tregs fail to increase during pregnancy in rats after IR injury, compared to the
significant rise observed in healthy pregnancy. Our central hypothesis will be tested by 3 aims: Aim 1
will test the hypothesis that failure to upregulate Tregs in pregnancy contributes to the adverse
pregnancy outcomes after IR injury. Aim 2 will test the hypothesis that reduced renal reserve after IR
results in uremia in pregnancy, and that the build-up of waste products with uremia inhibits Treg
expansion. Aim 3 will test the hypothesis that impaired NO bioavailability after IR injury results in
endothelial dysfunction and impaired uterine perfusion. The proposed studies will improve scientific
knowledge by providing the necessary pre-clinical foundation to elucidate the immune cell mechanisms
for adverse pregnancy outcomes after AKI and potentially identify novel immune targets.

## Key facts

- **NIH application ID:** 10116461
- **Project number:** 5K99HL150281-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Ellen E Gillis
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $110,938
- **Award type:** 5
- **Project period:** 2020-03-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116461

## Citation

> US National Institutes of Health, RePORTER application 10116461, Role of regulatory T cells in adverse pregnancy outcomes after ischemia reperfusion injury (5K99HL150281-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116461. Licensed CC0.

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