# B cells for treatment of ARDS

> **NIH NIH R56** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $610,236

## Abstract

Survivors of acute respiratory distress syndrome (ARDS) manifest pulmonary and neurological sequelae, as
clearly documented during the COVID-19 pandemic. The goal of this project is to ameliorate both pulmonary and
brain neuronal injury in ARDS and mitigate against long-term complications. Using a mouse model of hyperoxic
lung injury, we recently discovered that hyperoxia leads to a surprisingly profound depletion of pulmonary B cells,
with regulatory and memory B cell subsets being particularly vulnerable. B cell depletion has also been reported
in patients with ARDS. We aim to modulate inflammatory responses in ARDS by administering B cells that would
ameliorate this deficit and restore immune regulation. We now show that systemic administration of naïve B cells
has significant anti-inflammatory and tissue-protective effects in hyperoxic lung injury and that a fraction of these
B cells traffic to the lungs. Our central hypothesis is that adoptively transferred naïve B cells provide multiorgan
protection in hyperoxia-associated ARDS; we propose that this is achieved by trafficking to the sites of tissue
injury to restore immune regulation and suppress inflammatory responses in IL-10 and/or adenosine-dependent
manner. In Aim 1, we will study the efficiency of B cell homing to the lungs and brain and characterize the
phenotype(s) of B cells that home in these inflamed sites. In Aim 2, we will identify the immunomodulatory effects
of adoptively transferred B cells in the lungs and brain and study their dependence on B cell-derived non-Ig
factors including IL-10 and adenosine. In Aim 3, we will determine the effects of syngeneic and allogeneic B cell
therapy on long-term pulmonary and neurologic outcomes. Understanding long-term outcomes after allogeneic
B cell therapy will be critical for future translation of this therapy into clinical practice. The results of these
proposed experimental studies will direct our further research into B cell therapy for ARDS. Our studies may
have substantive translational impacts, in identifying novel therapeutic targets for treating patients with this highly
significant and increasingly common clinical problem.

## Key facts

- **NIH application ID:** 11175768
- **Project number:** 1R56HL175336-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Dusan Hanidziar
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $610,236
- **Award type:** 1
- **Project period:** 2024-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11175768

## Citation

> US National Institutes of Health, RePORTER application 11175768, B cells for treatment of ARDS (1R56HL175336-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11175768. Licensed CC0.

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