# Cis-regulatory mechanisms governing RORgt expression in type 3 lymphocytes

> **NIH NIH F31** · DUKE UNIVERSITY · 2024 · $48,974

## Abstract

ABSTRACT
Type 3 lymphocytes include group 3 innate lymphoid cells (ILC3),
IL-17-producing γδ T cells (Tγδ17), and
T
helper 17
(
TH17) cells and are crucial for maintaining mucosal barrier defenses against extracellular bacteria
and fungi. Nonetheless, dysregulated type 3 lymphocyte responses have been implicated in the pathogenesis
of several autoimmune diseases, such as inflammatory bowel disease, Crohn's disease, and multiple sclerosis.
ILC3,
Tγδ17, and
TH17 cells are defined by their shared expression of the lineage-defining transcription factor
RORγt (Rorc(t)), which facilitates key inductive events during the development and differentiation of these cell
types towards the type 3 lymphocyte lineage. The trans-acting factor networks that cooperatively regulate the
formation of the type 3 lymphocyte cell types have been well characterized, however, the cis-regulatory
elements (CREs) that control the development and differentiation of type 3 lymphocytes remain less defined
Therefore, we are proposing a comprehensive assessment of the CREs controlling the expression of the
Rorc(t) locus across the type 3 lymphocyte lineage
cell types. To this end, we will
(i) identify the CREs
governing Rorc(t) expression using a high-throughput CRISPRi knockdown screen; (ii)
evaluate the activity of
Rorc(t) CREs using a retroviral massively parallel STARR-seq reporter assay; (iii) and determine the functional
role of putative CREs for the expression of Rorc(t)
in the
ILC3,
Tγδ17, and
TH17
cell types.
Altogether, the
experiments outlined in this proposal will expand our understanding of the cis-regulatory mechanisms
governing type 3 lymphocyte development and identity.

## Key facts

- **NIH application ID:** 10818845
- **Project number:** 1F31AI181082-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Naren U Mehta
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818845

## Citation

> US National Institutes of Health, RePORTER application 10818845, Cis-regulatory mechanisms governing RORgt expression in type 3 lymphocytes (1F31AI181082-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10818845. Licensed CC0.

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