New Target for Lung Scarring Treatment Found

Researchers at the University of Calgary studying a lethal lung disease called pulmonary fibrosis have found that neurons known to help detect pain are also critical for reducing harmful lung inflammation that leads to the disease.

Pulmonary fibrosis, also called lung scarring, is uncommon but it's hard to treat and most people die within five years of diagnosis. Research to date has focused on how the lung lining gets damaged and the body's attempts to repair the issue. The role of neurons—a complex network of cells within the nervous system that send messages between the brain, spinal cord and through the body—and the immune system has received less study.

Now a research team led by Cumming School of Medicine (CSM) physician-scientist Dr. Bryan Yipp, MD, has found specific nerve cells that normally detect pain also help control inflammation during lung fibrosis.

The team's study detailing the discovery, titled "Nociceptor neurons suppress alveolar macrophage-induced Siglec-F+ neutrophil-mediated inflammation to protect against pulmonary fibrosis," is published in the journal Immunity.

"Our research into the role of the nervous system in lung diseases is new and our discovery opens up the possibility of using neurological therapies to treat lung diseases," says Yipp. "Diseases such as seizures and mood disorders are currently being treated with electrical stimulation of nerves. Our findings show the same nerves being treated with electrical devices are the ones responsible for lung protection, so it is conceivable that boosting their function could improve the scarring."

Nerve cells in the lungs normally detect pain and foreign particles, inducing cough. Using mice, researchers found those cells also help protect the lungs by keeping potent inflammatory cells in check. When these nerve cells were removed—either through drugs or genetic manipulation—the inflammatory cells became dysregulated, and lung damage worsened.

Without the protective nerve cells, immune cells in the lungs (called alveolar macrophages) started producing a molecule involved in nerve communications called a neuropeptide, which they normally do not make. This unusual production of a nerve communication molecule drove inflammatory lung damage.

"When we blocked the neuropeptide, named VIP, or removed the gene that makes it in the dysfunctional macrophages, the lung damage improved along with the harmful inflammation. But when VIP was added, the damage got worse again," says first author Dr. Carlos Hiroki, Ph.D., whose doctoral thesis investigated the impact of nerve cells on pulmonary fibrosis for the past five years.

Each year, about 2,500 people in Canada die from lung scarring and about 30,000 people live with the disease. The Yipp lab is working to better understand lung scarring so that new treatments can be developed.