# CD4 T cell stemness and inflammatory bowel disease

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $385,954

## Abstract

PROJECT SUMMARY/ABSTRACT
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that results from a loss in intestinal
homeostasis between the commensal microbiota and the immune system. Importantly, the etiology of IBD
remains unknown, although numerous studies have demonstrated a central role for CD4 T cells in the induction
of IBD. A tremendous amount of research has been performed to understand the functional aspects of the CD4
T cells that mediate the pathology and symptoms associated with IBD, and many of the currently approved
therapies, as well as a number of treatments in clinical trials, target these properties. Still, there is not a cure for
either Crohn’s Disease (CD) or Ulcerative Colitis (UC), and this may be in part because little is known regarding
how pathogenic CD4 T cells perpetuate the chronicity of disease. In recent years, the importance of T cell
stemness has emerged as a critical parameter that sustains protective and pathogenic cell mediated immunity.
During chronic intestinal inflammation, we observe that effector CD4 T cells with stem-like properties are able to
both sustain and confer disease and that these cells preferentially express ST6Gal-I-dependent α2-6 linked sialic
acids on the cell surface. In addition, we find that ST6Gal-I sialylation of N-glycans is important for expression of
the stemness-associated transcription factor, TCF1. These preliminary findings lead us to hypothesize that
effector CD4 T cell stemness promotes and sustains chronic intestinal inflammation in both mice and
humans, and that this intestinal inflammation in turn operates to preserve this unique population of T
cells. Furthermore, we postulate that ST6Gal-I mediated sialylation is central to effector CD4 T cell
stemness and the chronicity of disease. To test these hypotheses, we propose the following specific aims:
 Aim 1. Determine the impact of ST6Gal-I mediated sialylation on CD4 T cell driven intestinal inflammation
and CD4 T cell stemness.
 Aim 2. Determine the effect of the inflammatory intestinal environment on CD4 T cell stemness.
 Aim 3. Determine the contribution of stem-like effector CD4 T cells to chronic intestinal inflammation.
Collectively, these studies are designed to provide new information regarding how CD4 T cell stemness
impacts the chronicity of IBD. Moreover, findings that result from this application will illustrate how the
composition of the commensal microbiota, as well as post-translational modification of cell surface proteins,
specifically N-glycan sialylation, regulates CD4 T cell pathogenicity and stemness during chronic intestinal
inflammation.

## Key facts

- **NIH application ID:** 10237294
- **Project number:** 5R01DK125870-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Laurie Ellen Harrington
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,954
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237294

## Citation

> US National Institutes of Health, RePORTER application 10237294, CD4 T cell stemness and inflammatory bowel disease (5R01DK125870-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10237294. Licensed CC0.

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