# Macrophage phenotype and COPD severity

> **NIH NIH F32** · JOHNS HOPKINS UNIVERSITY · 2020 · $70,880

## Abstract

The overall objective of this NRSA Individual Fellowship is to develop skills that will allow the
candidate to become a physician-scientist and pursue an academic research career focused on
translational investigation of airways disease. The applicant and his mentors have devised a training
approach that includes both research and didactic instruction. This approach will establish the knowledge
and intellectual framework essential for a successful research career. The proposal concerns chronic
obstructive pulmonary disease (COPD). COPD is the fourth leading cause of death in the United States.
Despite the profound morbidity and mortality, the specific immunologic mechanisms are yet to be fully
elucidated.
 Recent data suggest the macrophage is at the forefront as it plays a critical role in host defense and
eventually tissue repair. Many studies have characterized macrophages from human COPD patients compared
to healthy subjects identifying different levels of surface markers and cytokine expression suggesting distinct
macrophage function in COPD patients. In particularly, macrophages from COPD patients compared to healthy
controls exhibit reduced expression of surface markers important for immunity (adhesion molecules, antigen
presentation molecules and recognition markers), as well as alterations in cytokine production. Although
impaired macrophage cytokine release has been associated with increased exacerbations and worse severity
of COPD, the specific macrophage surface markers and cytokines associated with increased COPD morbidity
remains unknown. Our preliminary analysis demonstrates reduced airway macrophage CD80 expression and
increased TGF-1 is associated with worse respiratory symptoms and worse lung function, respectively. It is
not known if this association holds true for other measures of COPD morbidity and exacerbation frequency.
Additionally, the regulation of airway macrophage CD80 expression remains poorly understood. Our intriguing
preliminary data indicates a reverse correlation between TGF-1 production and CD80 expression.
 In Specific Aim 1, the candidate will examine the association of (a) airway macrophage CD80
expression and (b) TGF-β1 production with COPD morbidity (lung function, exacerbation risk and respiratory
symptoms). Multicolor flow cytometry will be used to determine macrophage surface marker expression and
intracellular cytokine production. We hypothesize that both reduced CD80 expression and increased TGF-β1
production are independently associated with worse COPD morbidity. Specific Aim 2 will define the TGF-
β1/CD80 axis of the airway macrophage. Exposure to TGF-β1 and TGF-β1 blocking antibodies ex vivo will
elucidate if this biologic pathway can be modulated. These experiments will explore the immunologic
mechanisms leading to worse morbidity in COPD patients with the ultimate hope of personalizing therapy
for those with low CD80 expression and potentially identifying new therapeutic targets.

## Key facts

- **NIH application ID:** 10001338
- **Project number:** 5F32HL149258-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Vickram Tejwani
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,880
- **Award type:** 5
- **Project period:** 2019-07-29 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001338

## Citation

> US National Institutes of Health, RePORTER application 10001338, Macrophage phenotype and COPD severity (5F32HL149258-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001338. Licensed CC0.

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