Researchers at the University of Calgary studying a lethal lung disease called pulmonary fibrosis have found neurons, which were 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 had less study.
That is until a research team led by Cumming School of Medicine (CSM) physician-scientist Dr. Bryan Yipp , MD, found specific nerve cells that normally detect pain, also help control inflammation during lung fibrosis. An article – Nociceptor neurons suppress alveolar macrophage-induced Siglec-F+ neutrophil-mediated inflammation to protect against pulmonary fibrosis – detailing the discovery was published in the journal Immunity in August.
“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,” says Yipp.
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, PhD, 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.
This research received funding from the Canadian Institutes of Health Research (CIHR). The team will continue the study after receiving additional CIHR grant funding earlier this year. The research also benefited from use of the CSM’s Nicole Perkins Microbial Communities Core Labs flow cytometry core facility.
September is Pulmonary Fibrosis awareness month , a global event designed to raise awareness and support those affected by the disease.
Bryan Yipp, MD, is an intensivist and professor in the Department of Critical Care Medicine at the Cumming School of Medicine (CSM). He is a member of the Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases at the CSM.
Carlos Hiroki, PhD was postdoctoral fellow in the Dr. Yipp’s lab at the CSM. He is a graduate of the Beverley Phillips Rising Star training program in the CSM’s Snyder Institute for Chronic Diseases and a Canadian Lung Association scholarship recipient.