# Endothelial antigen presentation to T cells as a pathogenic mechanism in influenza-induced acute lung injury.

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $399,750

## Abstract

Endothelial antigen presentation to T cells as a pathogenic mechanism in influenza-induced acute lung
injury.
ABSTRACT
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a form of acute respiratory failure with
substantial mortality, characterized by massive loss of lung vascular barrier function due to excessive
inflammation, endothelial cell injury and death. Up to 20% of hospitalized patients with an influenza infection
develop ALI or ARDS and require mechanical ventilation. Unfortunately, there are no targeted therapies available
to prevent death secondary to ALI/ARDS. Therefore, it is imperative to understand the mechanisms by which
the influenza virus induces ALI and identify novel therapeutic targets. Lung epithelial injury has been well studied
in influenza infections, however the mechanisms of endothelial injury induced by influenza virus are still poorly
understood despite the fact that endothelial injury is a central feature of ALI/ARDS. Besides their role in
maintaining vascular barrier function, vascular endothelial cells (ECs) play an important role in regulating
inflammation. Our novel supporting data indicate that lung ECs consist of at least two major subpopulations –
pro-inflammatory ECs and pro-regenerative or developmental ECs during baseline conditions. Developmental
lung EC express the developmental transcription factor Sox17 which regenerates the injured endothelium during
infections. Inflammatory lung ECs, on the other hand, express low levels of Sox17 and instead express higher
levels of the major histocompatibility complex (MHC) class I and II molecules. H1N1 infection significantly
upregulates the expression of MHC class I and II molecules in ECs. The infection also significantly increases the
number of CD8+ cytotoxic T lymphocytes in the lung. Therefore, we hypothesize that inflammatory ECs act as
antigen presenting cells and present antigens to T lymphocytes and thus promote acute lung injury. We will study
whether expression of developmental and regenerative transcription factor Sox17 prevents the activation of
inflammatory signaling and antigen presentation. We will also assess whether the lung ECs present antigens to
CD8+ and CD4+ T lymphocytes by MHC class I and II molecules during H1N1-induced ALI. Finally, we will study
whether the activation of CD8 cytotoxic T cells induces EC death via the release of Granzyme B and cleavage
of its intracellular target Gasdermin E during H1N1-induced ALI. Here, we propose a novel mechanism of
endothelial cells as antigen presenting cells in influenza-induced ALI/ARDS. Unravelling this mechanism will
provide new insights and identify novel therapeutic targets into virus-induced ALI.

## Key facts

- **NIH application ID:** 10182393
- **Project number:** 1R01HL157489-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Lianghui Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $399,750
- **Award type:** 1
- **Project period:** 2021-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10182393

## Citation

> US National Institutes of Health, RePORTER application 10182393, Endothelial antigen presentation to T cells as a pathogenic mechanism in influenza-induced acute lung injury. (1R01HL157489-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10182393. Licensed CC0.

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