# CD45 mediated regulation of PMN function during intestinal inflammation

> **NIH NIH R56** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $497,370

## Abstract

Abstract:
It has been well documented that disease activity in inflammatory mucosal diseases including inflammatory
bowel disease is linked to the transepithelial migration of neutrophils through the mucosal epithelium and
ultimately into the intestinal lumen. Co-incident with massive luminal influx of neutrophils is uncontrolled release
of toxic tissue damaging metabolites that contribute to mucosal and/or transmural injury including edema, loss
of goblet cells, decreased mucus production, crypt cell hyperplasia, ulceration and crypt abscess formation. The
complex signaling mechanisms that regulate neutrophil transepithelial migration and inflammatory function in
mucosal tissues have not been fully elucidated even though excessive neutrophil activation is heavily implicated
in disease pathology of IBD and other inflammatory disorders. Preliminary data identifies the tyrosine
phosphatase CD45 as an important regulator of neutrophil intestinal infiltration and inflammatory function. This
proposal will determine effects of neutrophil specific loss of CD45 on intestinal inflammation and repair using
novel neutrophil specific CD45 deficient mice. We will also determine how CD45 phosphatase activity regulates
neutrophil intracellular signaling pathways and inflammatory effector functions including migration,
degranulation, and superoxide release. Finally using specific antibodies and glycan binding proteins we will
determine how specific CD45 isoforms and glycoforms can be targeted to regulate neutrophil activation and
inflammatory responses. Elucidating beneficial effects of targeting neutrophil CD45 phosphatase activity during
colitis will help to develop novel strategies to ameliorate pathological intestinal inflammation.

## Key facts

- **NIH application ID:** 11166891
- **Project number:** 1R56DK140172-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jennifer C Brazil
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,370
- **Award type:** 1
- **Project period:** 2024-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11166891

## Citation

> US National Institutes of Health, RePORTER application 11166891, CD45 mediated regulation of PMN function during intestinal inflammation (1R56DK140172-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11166891. Licensed CC0.

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