# Transcriptional Regulation of Innate-Like T Cells

> **NIH NIH R37** · UNIVERSITY OF CHICAGO · 2020 · $525,030

## Abstract

Unlike adaptive lymphocytes, innate and innate-like lymphocytes acquire stereotypic polarized helper effector
programs during development, independently of pathogen exposure and prior to taking up residence in
peripheral tissues where they function as first line of defense against aggressions by pathogens, allergens,
tumors and injuries. Our group has established that PLZF encoded by Zbtb16 is a signature master
transcription factor directing the acquisition of innate effector programs across many of these innate lineages,
including CD1d-restricted NKT cells, MR1-restricted MAIT cells, γδ T cell subsets and innate lymphoid cells
(ILC).
While the genetic mechanisms of activation of this effector program by PLZF is now well dissected, this project
specifically focuses on the conditions leading to the expression of PLZF during lymphoid development. Since
PLZF is necessary and sufficient for activation of the innate effector program, the central question of this
proposal revolves around the regulation of PLZF expression itself. Our general hypothesis is that specific
transcriptional regulatory networks act upon distinct or partially overlapping sets of enhancers to govern Zbtb16
expression in different innate lineages. We will use recent technical advances that allow broad mapping of
genomic regions of chromatin accessibility (ATAC-seq) and their systematic deletions (Crispr-Cas9) to
comprehensively dissect the enhancer landscape (regulome) of Zbtb16 in vivo (Specific Aim 1). Through
advanced computational motif analysis, we will then identify candidate transcription factors (trans-regulation)
and evaluate their contributions to the regulation of Zbtb16 expression (Specific Aim 2). Finally, we will
examine the mutual antagonism between PLZF and Bach2, to understand how they reciprocally regulate the
innate and adaptive pathways of lymphocyte development (Specific Aim 3). Collectively, these specific aims
address the fundamental dichotomy between innate and adaptive lymphocyte development and will generate
knowledge and tools to selectively manipulate their properties for therapeutic benefit in health and disease.

## Key facts

- **NIH application ID:** 9980264
- **Project number:** 5R37AI038339-24
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** ALBERT S. BENDELAC
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $525,030
- **Award type:** 5
- **Project period:** 1996-04-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980264

## Citation

> US National Institutes of Health, RePORTER application 9980264, Transcriptional Regulation of Innate-Like T Cells (5R37AI038339-24). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9980264. Licensed CC0.

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