# Cross-talk between lung natural killer cells and dendritic cells in COPD

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the United States,
yet there are no current therapeutic treatments to halt disease progression. Airway inflammation and
parenchymal destruction are central to the pathogenesis of COPD. Numerous inflammatory cell
types have been implicated in COPD but an understanding of how these cell types contribute to lung
destruction is lacking. Natural killer cells (NKs), an important component of the innate immune
system, are known for their ability to detect and kill stressed, infected, or damaged cells. Our data
demonstrate that NKs from the lungs of COPD patients are able to kill more autologous lung epithelial
cells than NKs from the lungs of smokers without COPD. Similarly, in a murine cigarette smoke (CS)
exposure model, lung NKs from CS-exposed mice are more cytotoxic towards autologous epithelial
cells than air-exposed NKs. Therefore understanding the processes that control NK activation could
identify therapeutic targets. In order to become activated, NKs undergo a priming phase, typically
mediated by dendritic cells (DCs). We propose to use both human tissues and our murine CS-
exposure model to demonstrate that mature DCs are necessary for NK priming. We will also
investigate the mechanism of killing by focusing on the steps leading to cytotoxicity: adhesion to
target cell, polarization of lytic granules, and degranulation. Finally, we will determine whether lung
NK production of IL-22, a cytokine capable of inducing epithelial cells to make pro-inflammatory
molecules, is also contributing to COPD pathology. To demonstrate the relevance of our findings to
COPD, we also propose to study NKs and DCs from human lung tissue. Our goal is to translate
results from these murine and human studies into clinically relevant discoveries regarding NK
cytotoxicity in COPD pathogenesis.

## Key facts

- **NIH application ID:** 9858246
- **Project number:** 5I01CX001553-07
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Christine M Basmajian
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858246

## Citation

> US National Institutes of Health, RePORTER application 9858246, Cross-talk between lung natural killer cells and dendritic cells in COPD (5I01CX001553-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858246. Licensed CC0.

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