# Transcriptional Regulation of Innate T cell fate

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2022 · $194,375

## Abstract

Project Summary
InnateT cells are a collection of T cells withimportant regulatory functions that have a crucial role in immunity
towards tumors, bacteria, viruses, and in cell-mediated autoimmunity. Due
large quantities of cytokines upon activation,
immune
response
populations
glycolipid
cells
T
commitment
to
innate T cells act as bridges between the innate and adaptive
systems a nd ontribute greatly In mice, this swiftness of
reflects their acquisition f functionality during their development in the thymus. Three major
within the innate T cell group are recognized namely, the invariant NKT cells that recognize
antigens presented by non-polymorphic CD1d molecules, the mucosal associated invariant T (MAIT)
that recognize vitamin metabolites presented by the non-polymorphic MR1 molecules, and the certain 
cells which antigen specificities remain uncertain. We have established an in vitro system t hat mimics the
of double positive precursor cells to the innate T cell lineage and we propose to
their ability to promptly secrete
c to immune regulation and host protection.
o
,
deconstruct the
early transcriptional and epigenetic events that accompany this fate commitment (Aim 1). In this way, we will
identify
manipulation
early factors that influence innate T cell development, providing the possibility for selective
of innate T cell lineage specification. We will then investigatewhether human innate T cells
acquire an innate-like transcriptional program in the thymus similarly to their mouse counterparts and whether
this program is shared between the two species. To do so, we will profile the transcriptomes of iNKT and MAIT
cells purified from neonatal human thymi at the single cell level. In addition, we will extend our knowledge of
innate T cell lineage commitment by also studying CD1a-restricted T cells, which do not exist in mice (Aim 2).
Given their capacity to link key inflammatory axes of innate and adaptive immunity, a better understanding of
the molecular basis underpinning innate T cell development and plasticity, and how much this feature accounts
for their pathophysiological roles, is critical for developing novel therapeutic approaches.

## Key facts

- **NIH application ID:** 10450153
- **Project number:** 5R21AI163454-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Laurent Gapin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2021-07-14 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450153

## Citation

> US National Institutes of Health, RePORTER application 10450153, Transcriptional Regulation of Innate T cell fate (5R21AI163454-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450153. Licensed CC0.

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