# PLZF expression in adipose resident natural killer T cells

> **NIH NIH R21** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2022 · $196,250

## Abstract

Project Summary
Adipose tissue is a site where the immune system and metabolic pathways intersect. Adipocytes are now
recognized as antigen presenting cells for lipids and likely directly activate natural killer T cells (NKT cells) via
CD1d. NKT cells are potent modulators of the immune system that are able to regulate the function of other
cell types largely by their capacity to rapidly produce large amounts of a wide variety of cytokines. Recent data
show that adipose resident NKT cells (arNKT cells) modulate diet-induced weight gain and influence
metabolism. When eating a calorically balanced diet, arNKT cells appear to encourage adipocytes to maintain
a healthy tissue environment and prevent insulin resistance.
Nearly all of the innate-like functions of NKT cells are dependent upon the BTB-ZF transcription factor, PLZF
(zbtb16). Therefore, it is surprising that arNKT cells do not express PLZF. To our knowledge, this is the only
population of NKT cells that does not continuously express the transcription factor. Chronic inflammation is
associated with weight gain and subsequent metabolic disease. arNKT cells were shown to induce an anti-
inflammatory response both by modulating macrophage functions and by impacting the frequency, proliferation
and function of FoxP3-expressing Tregs. We propose that altered PLZF expression will impact these arNKT
cell functions, which in turn, will alter the metabolism of white adipose tissue. Our studies will determine if
changes in PLZF expression in arNKT cells alters their ability to control obesity and metabolic changes.
We will use an innovative array of genetically modified mouse models that allow for variation in the levels of
PLZF expression. We hypothesize that PLZF protein levels are essential for the control of arNKT cell functions
and if the levels are altered, the onset of obesity and metabolic disease will increase. Data supporting this
conclusion will lead to future studies to determine if variability in PLZF expression in humans is potentially a
contributing factor to obesity. Importantly, analysis of arNKT cells that do not function correctly is expected to
reveal new information about the mechanisms by which arNKT cells normally function.

## Key facts

- **NIH application ID:** 10364677
- **Project number:** 5R21AI159066-02
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Derek B. Sant'Angelo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2021-03-08 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364677

## Citation

> US National Institutes of Health, RePORTER application 10364677, PLZF expression in adipose resident natural killer T cells (5R21AI159066-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364677. Licensed CC0.

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