# Molecular Mechanisms of Invariant Natural Killer T Cell Differentiation

> **NIH NIH R56** · UNIVERSITY OF CHICAGO · 2022 · $324,666

## Abstract

Project Summary
Invariant Natural Killer T (iNKT) cells are T lymphocytes that express a semi-invariant T cell
receptor (TCR) and exist in a primed effector state capable of making numerous cytokines
within minutes after activation. iNKT1 cells develop in the thymus and migrate as immature cells
to peripheral lymphoid and non-lymphoid organs where they reside as tissue-resident sentinels
that protect against invading pathogens. Here we describe the transcription factor Ets1 as a
central regulator of the development, adhesion, migration, and NK cell-associated gene
programs of iNKT1 cells that control their tissue residency, localization, and function. We
propose experiments to investigate the relevance of these programs to iNKT1 cell development,
trafficking, location and function as well as experiments to identify the molecular basis for Ets1-
mediated regulation of these programs in the thymus, liver and spleen. Given the conservation
of tissue residency and adhesion programs across lymphocytes, we propose that our data will
provide not only significant insight into the mechanisms controlling iNKT1 cell location but also
in other innate and adaptive lymphocytes.

## Key facts

- **NIH application ID:** 10627307
- **Project number:** 2R56AI123396-06A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** BARBARA L. KEE
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $324,666
- **Award type:** 2
- **Project period:** 2016-12-19 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10627307

## Citation

> US National Institutes of Health, RePORTER application 10627307, Molecular Mechanisms of Invariant Natural Killer T Cell Differentiation (2R56AI123396-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10627307. Licensed CC0.

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