# Mechanisms of E protein transcription factor-dependent iNKT cell expansion and differentiation

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $399,048

## Abstract

Project Summary
Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that sit at the boarder
of adaptive and innate immunity. They have highly restricted T cell receptors (TCRs) that
detect glycolipid antigen presented by the non-classical MHC molecule CD1d and they
respond rapidly to antigen or cytokine stimulation. NKT cells play an important role in
anti-microbial immune responses and because of their rapid production of multiple
cytokines they are being considered as therapeutic agents in cancer and other diseases.
NKT cells acquire their effector phenotype as a consequence of their unique mechanism
of selection and differentiation in the thymus. The range of effector fates that NKT cells
can acquire is only beginning to be appreciated but the mechanisms controlling NKT cell
effector fate choice are completely unknown. Our research is directed at understanding
the molecular mechanisms that control iNKT cell development with a focus on the E
protein transcription factors, their inhibitors the ID proteins, and their downstream targets.
These proteins are critical regulators of iNKT cell numbers and effector cell fate choice.
In this grant application we propose experiments to determine the requirements for E2A
in iNKT cell development an the consequences of over- and under-expression of two
putative E2A target genes, Lef1 and Bcl6. Our studies will have a major impact on our
understanding of how NKT cell number and function is regulated. In addition, our studies
will provide insight into mechanisms to manipulate NKT cell effector fate and thereby
alter immune responses at their inception.

## Key facts

- **NIH application ID:** 9824544
- **Project number:** 5R01AI123396-04
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** BARBARA L. KEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,048
- **Award type:** 5
- **Project period:** 2016-12-19 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824544

## Citation

> US National Institutes of Health, RePORTER application 9824544, Mechanisms of E protein transcription factor-dependent iNKT cell expansion and differentiation (5R01AI123396-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9824544. Licensed CC0.

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