# Molecular mechanisms underlying HIV related intestinal epithelial barrier dysfunction

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $105,689

## Abstract

Abstract
Compromised intestinal permeability leads to release of epithelial cytokines and antigenic exposure to underlying
immune cells. Cytokine release by immune cells in turn perturbs intercellular junction proteins that are crucial for
formation of an intact intestinal epithelial barrier. Our data suggest that co-incubation of IECs with HIV-1 infected
T cells results in a Nef dependent loss of IEC barrier integrity due to increased epithelial expression of TNFa.
Past studies, including work from our group, suggest that pro-inflammatory cytokines disrupt IEC function with
preliminary data indicating that TNFa plays an important role HIV-associated intestinal pathology. Interestingly,
our research has identified pro-repair functions of TNFa in wounded IEC. At initial glance, intestinal epithelial
barrier disruption and enhanced wound repair seem disconnected and even contradictory, but these effects may
be explained by signaling mechanisms that result in loosening of epithelial junctions to enhance migration to
repair injuries resulting from the inflammatory response. Thus, a leaky barrier as well as increased migration of
IEC are interconnected functions triggered by soluble mediators such as TNFa. As the parent grant focuses on
barrier dysfunction, this supplemental proposal aims to look at the complementary effects of inflammatory
mediators on IEC migration as it relates to repair. The overarching hypothesis is that cytokines such as TNFa
impair barrier by altering expression of junctional proteins which in turn increases permeability while promoting
IEC migration

## Key facts

- **NIH application ID:** 10630643
- **Project number:** 3R01DK129058-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kathleen L. Collins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $105,689
- **Award type:** 3
- **Project period:** 2021-09-10 → 2024-09-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630643

## Citation

> US National Institutes of Health, RePORTER application 10630643, Molecular mechanisms underlying HIV related intestinal epithelial barrier dysfunction (3R01DK129058-02S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10630643. Licensed CC0.

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