# Regulation of the type 1 program during ILC3 plasticity

> **NIH NIH F31** · DUKE UNIVERSITY · 2021 · $38,290

## Abstract

Innate lymphoid cells (ILCs) are tissue-resident immune cells that contribute to tissue immunity, homeostasis,
and inflammation. ILCs lack antigen specificity and are preprogrammed for effector function during ontogeny,
allowing for rapid cytokine secretion upon stimulation. Group 3 innate lymphoid cells (ILC3s), defined by the
lineage-defining transcription factor RORgt and IL-22 production, are a heterogenous group of ILCs that display
marked plasticity and are predominantly found in the intestinal lamina propria. CCR6- ILC3s are mediators of
intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully
convert into ‘ex-ILC3’ ILC1s. Notably, the conversion of ILC3s to ILC1-like cells also takes place in human
mucosal tissues in vitro and in vivo. Although providing flexibility during infection, ILC3 plasticity is also
associated with immune-related pathology. In particular, enhanced ILC3 to ILC1 conversion has been
implicated in Crohn’s disease based on skewing towards IFNg+ ILC1s at the expense of ILC3 cells. The
molecular mechanisms governing such plasticity are still largely undefined. In our recent work, we defined c-
Maf as an essential regulator of CCR6- ILC3 homeostasis and plasticity that controls the balance of DN and
NKp46+ ILC3s and limits physiological conversion to an ILC1 state. Accordingly, loss of c-Maf resulted in a
type 1 skewing, marked by increased levels of T-bet and IFNg, alongside reduced expression of RORgt and IL-
22 within the CCR6- ILC3 compartment. Taking advantage of the role of c-Maf as a gatekeeper of ILC3
plasticity, this proposal will define the molecular mechanisms by which c-Maf restricts the type 1 program and
promotes ILC3 stability through integration of type 1-associated transcription factor occupancy and chromatin
landscape data to understand the direct versus indirect roles of c-Maf. Additionally, we will identify cis-
regulatory elements in Tbx21 using low and high-throughput reporter assays and subsequently determine their
contribution to ILC3 to ILC1 conversion in vivo through CRISPR/Cas9 deletion. Taken together, the
experiments proposed in this grant will deepen our understanding of the important trans-acting factors and cis-
regulatory elements governing ILC3 plasticity.

## Key facts

- **NIH application ID:** 10128182
- **Project number:** 5F31AI152457-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Morgan Elizabeth Parker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,290
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128182

## Citation

> US National Institutes of Health, RePORTER application 10128182, Regulation of the type 1 program during ILC3 plasticity (5F31AI152457-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128182. Licensed CC0.

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