# Regulation and Maintenance of Adipose Tissue T cells

> **NIH NIH K99** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $90,000

## Abstract

ABSTRACT
Adipose tissue (AT) is an active metabolic organ that contains a network of immune cells whose crosstalk
regulates adipose tissue homeostasis. In response to obesity, these immune cells can become activated,
expand, and secrete adipokines and pro-inflammatory cytokines that modify local and systemic insulin
sensitivity and contribute to the development of metabolic dysfunction and type 2 diabetes. Promotion and
maintenance of adipose tissue inflammation in the obese state has been shown to involve the activation of
adipose tissue T cells (ATT), which potentiate the activity of pro-inflammatory adipose tissue macrophages
(ATMs) in mouse models of obesity. There is a fundamental gap in our understanding of the mechanisms by
which ATTs are maintained, their diversity relative to other T cell subsets, and the signals to which ATTs
respond during adipose tissue remodeling and expansion. Our preliminary data assessing early ATT kinetics
demonstrated that ATTs proliferate in response to the rapid AT expansion induced by short-term high-fat diet
(HFD) feeding. Timepoints assessed in these experiments precede the substantial infiltration of pro-
inflammatory ATMs associated with the obese state, suggesting ATTs play vital roles in the initiation of AT
inflammation observed in the obese state. This proposal seeks to test the hypothesis that ATT proliferation in
response to short-term HFD feeding requires signals from antigen presenting cells (APCs). Further, the
proposed research will interrogate the establishment of memory ATT and the determinant which drive the
priming of their responses to AT changes in the obese state. Lastly, the PI’s prior research uncovered a unique
population of TCRαβ CD3+ CD4- CD8- double negative (DN) ATTs and will test the hypothesis that DN ATTs
possess an immunoregulatory phenotype and function in maintaining AT homeostasis and controlling effector
ATTs during development of obesity. To test these hypotheses, the proposed project will pursue the following
Aims during the K99 phase of this award: 1) To determine driver(s) of ATT proliferation during short-term HFD
feeding and 2) to identify phenotype and function of DN ATTs in the lean and obese state. During this time, the
PI will receive research training in nutrient metabolism in mice, bioinformatics and sequencing analysis, and
translational research in obesity and diabetes. During the independent R00 phase, the PI will continue these
Aims and seek to 3) determine establishment of resident memory ATTs and signals required for their induction
and maintenance. Completion of this work will have significant impact on identification of the regulators of ATT
functions in lean and obese states and elucidate novel targets to suppress obesity-associated AT inflammation
mediated by ATT responses. Training in proposed techniques outlined in the K99 phase will ensure successful
formation of the PI’s independent research program centering on obesity-associated inflammation and
...

## Key facts

- **NIH application ID:** 10911329
- **Project number:** 5K99DK136934-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ramiah Donesha Jacks
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $90,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911329

## Citation

> US National Institutes of Health, RePORTER application 10911329, Regulation and Maintenance of Adipose Tissue T cells (5K99DK136934-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10911329. Licensed CC0.

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