# Characterization of a novel ILC-like population of adipose-resident cells

> **NIH NIH R21** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2020 · $198,750

## Abstract

Project Summary
In this application, we describe a population of adipose cells that appear to be ILC as they lack expression of
CD3, MHCII, and NK1.1. Interestingly, these ILC-like cells co-express high levels of the transcription factors
PLZF and RORt. The study of these newly identified adipose PLZF, RORt cells is the focus of this R21
application. Our colleague at Rutgers found that the FDA approved metabolic uncoupling anthelmintic
treatment, niclosamide ethanolamine (NEN), shows promise for the treatment of Type 2 Diabetes. NEN proved
to be highly effective in treating symptoms arising from two different mouse models of diabetes. This included
preventing weight gain, increased fasting blood glucose and basal plasma insulin. NEN also improved insulin
sensitivity in these models. We carried out exploratory experiments to determine if NEN treatment altered the
frequencies or phenotype of adipose resident lymphocytes after mice were fed high fat diet. The results of
these analyses led to the identification of the adipose PLZF,RORt ILC.
Of particular interest was that the adipose PLZF,RORt ILC from mice fed high fat diet expressed CD44,
suggesting activation in response to conditions associated with the onset of obesity and metabolic syndrome.
Remarkably, when treated with NEN, CD44 upregulation was prevented, suggesting that part of the
mechanism by which NEN prevents Type 2 Diabetes is immune system mediated. There is a growing
understanding that lymphocytes contribute to maintenance of an anti-inflammatory environment and
thermogenic programs in adipose tissues. The continued effort to define the function of all lymphocyte
subtypes in the fat will clearly be essential for understanding these processes. If successful, this grant will
identify a new lymphocyte population that, based upon preliminary data, might control adipose tissue immune
homeostasis and thermogenesis. Such cells types continue to open new possibilities for the treatment of a
major health problem.
In this R21 application we propose to study a novel population of innate-like cells that simultaneously express
high levels of PLZF and RORT. The characterization of this population of cells expressing two transcription
factors that display such specific and function-oriented expression in the immune system will greatly enhance
our understanding of the cellular subsets that regulate the adipose microenvironment. Of particular note here is
that this population expresses an activation-associated phenotype (increase in CD44 expression) in response
to high fat diet that is abrogated in response to treatment shown to diminish diet-induce metabolic
dysregulation. This drug (NEN) is already approved for use in humans for the treatment of helminth infection.
Therefore, successful completion of the experiments described in this proposal has the potential for rapid
translation to immunotherapy to combat obesity and metabolic diseases.

## Key facts

- **NIH application ID:** 9822957
- **Project number:** 5R21AI138505-02
- **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:** 2020
- **Award amount:** $198,750
- **Award type:** 5
- **Project period:** 2018-11-14 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822957

## Citation

> US National Institutes of Health, RePORTER application 9822957, Characterization of a novel ILC-like population of adipose-resident cells (5R21AI138505-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822957. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*