# A T cell STAT3/BATF-axis regulates intestinal γδ T cell homeostasis and disease

> **NIH NIH F31** · PURDUE UNIVERSITY · 2024 · $40,468

## Abstract

PROJECT SUMMARY
My long-term career goal is to do hypothesis-driven research as an independent investigator at a university
spanning basic and clinical immunology in inflammatory bowel diseases (IBD). In order to achieve this goal, I
have put together an advisory team composed of Dr. Matthew Olson (sponsor), Dr. Timothy Ratliff (co-sponsor),
Dr. Tzu-wen Cross (collaborator), Dr. Majid Kazemian (collaborator), Dr. Shihuan Kuang, and Dr. Wayne
Campbell to provide technical training for in vitro cell culture techniques, in vivo mouse models of intestinal
disease, and gnotobiotic training, as well as other professional development skills in scientific writing and
communication. My preliminary work outlined in this proposal has demonstrated that mice with conventional T
cell-specific deletions in two important T cell transcription factors, STAT3 and BATF, developed an aggressive
spontaneous colitis that was marked by a dysregulated microbiota and elevated numbers of γδ T cells in the
intestines similar to what is observed in human patients. Given that the current treatment options available for
IBD are not fully effective in long term treatment, my data indicate that disrupting this STAT3/BATF-axis through
targeting the dysregulated gut microbiota or γδ T cells may represent a novel therapeutic strategy. To further
understand this complex relationship between dysregulated gut microbiota and non-conventional γδ T cells in
IBD-like colitis, this proposal will address the following: (1) Elucidate the role of the microbiota in regulating
intestinal γδ T cell homeostasis during intestinal disease. 16S rRNA sequencing will be used to define shifts in
the microbial community in each mouse genotype. To determine if this microbiota is required and sufficient to
induce γδ T cell responses and disease we will treat animals with antibiotics and perform fecal microbiota
transfers into germ-free animals, respectively. (2) Determine the role of γδ T cells in driving IBD. Therapeutically,
I will treat mice with monoclonal antibodies that block γδ T cell receptor activation and monitor its impact on
inflammatory responses in the intestines and clinical disease development. In order to determine if γδ T cells
can confer disease, I will isolate γδ T cells from Stat3fl/flBatffl/flCd4Cre+ mice and transfer them into colitis
susceptible (Rag-/-) mice. The results of this proposal will further elucidate the role of γδ T cells in
Stat3fl/flBatffl/flCd4Cre+ mice, which may serve as useful model to study γδ T cells in IBD-like colitis. Given that
current therapies for IBD patients are only partially effective, the resulting data from this study and the
establishment of this unique mouse model of γδ T cells in IBD-like colitis will potentially identify novel therapeutic
targets to make a positive impact on the 6.8 million people living with IBD worldwide.

## Key facts

- **NIH application ID:** 10851705
- **Project number:** 5F31DK135369-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Nicole Anderson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,468
- **Award type:** 5
- **Project period:** 2023-08-21 → 2025-08-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851705

## Citation

> US National Institutes of Health, RePORTER application 10851705, A T cell STAT3/BATF-axis regulates intestinal γδ T cell homeostasis and disease (5F31DK135369-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10851705. Licensed CC0.

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