# Regulation of immune cell function by the PVAT microenvironment

> **NIH NIH P01** · MICHIGAN STATE UNIVERSITY · 2024 · $331,977

## Abstract

Project Summary – Project III
 Approximately 30% of U.S. adults have high blood pressure. Of particular concern, the prevalence of
hypertension-related deaths increased 23% from 2000 to 2013, which correlates with a concurrent increase in
the prevalence in obesity during this time. Adiposity increases an individual's risk for a number of diseases,
including hypertension and heart disease. Accordingly, high fat diet-induced hypertension is currently a
significant public health concern and a high priority. Thus, there is a critical need to elucidate the mechanisms
driving the development of adiposity-associated hypertension. Our preliminary data demonstrate that there is a
large immune cell population in perivascular adipose tissue and that there is a greater number of immune cells
per mg tissue in PVAT as compared to other adipose tissues. Furthermore, our data also demonstrate that the
PVAT microenvironment influences immune cell function. In particular, our results show mPVAT conditioned
media from healthy rats suppresses IL-2 secretion by activated T cells, which suggests that under homeostatic
conditions the PVAT microenvironment may serve to buffer T cell activation. Conversely, mPVAT conditioned
media from rats on a HF diet promotes the production of pro-inflammatory cytokines, such as GM-CSF, IFNγ
and IL-17a, by activated T cells. Notably, these effects are observed prior to the development of hypertension.
RNA-sequencing of the PVAT from these rats revealed a substantial increase in the expression of DPP-4, a
peptidase that acts as a costimulatory factor in T cells. We also found that DPP-4-specific inhibitors mitigated
the increase in IL-17a by PVAT-CM from HF diet-fed rats. These exciting preliminary results have led to our
central hypothesis that the PVAT microenvironment controls inflammation during homeostasis, while
conversely promoting inflammation early during the development of high fat diet-induced hypertension. We
propose to test this hypothesis through the following specific aims: 1. Determine the mechanism by which
PVAT promotes a pro-inflammatory environment early during the development of HF diet-induced
hypertension, while maintaining a semi-quiescent environment during health. We hypothesize that activation
of PPARγ by endogenous ligands causes inhibition of IL-2 secretion during homeostasis, whereas induction of
DPP-4 plays a role in promoting pro-inflammatory cytokine production during high fat diet-induced
hypertension. and 2. Determine the role of CD4 and CD8 T cells in the development of HFD-induced
hypertension and inflammation. We propose to perform T cell depletion in combination with adoptive transfers
to determine the role of T cells in high fat diet-induced hypertension.

## Key facts

- **NIH application ID:** 10747969
- **Project number:** 5P01HL152951-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Cheryl Elizabeth Rockwell
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $331,977
- **Award type:** 5
- **Project period:** 2021-12-22 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747969

## Citation

> US National Institutes of Health, RePORTER application 10747969, Regulation of immune cell function by the PVAT microenvironment (5P01HL152951-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10747969. Licensed CC0.

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