Scientists discover treatment target for pulmonary fibrosis

July 11, 2017 by Anna Williams
The figure demonstrates how human pathology (top) can be digitized for precision medicine (bottom). “Before, we were limited to histologic analysis of lung tissues. Now we can measure the expression of every gene and every cell within that lung and actually digitize that biology,” Budinger said. Credit: Northwestern University

In new research published in the Journal of Experimental Medicine, Northwestern Medicine scientists have demonstrated that a unique population of immune cells plays a key role in the development of pulmonary fibrosis. They also showed that targeting such cells could lead to new treatments for the disease.

The study, a collaboration across multiple divisions, departments and schools at Northwestern, was led by Scott Budinger, MD, chief of Pulmonary and Critical Care in the Department of Medicine, and Harris Perlman, PhD, chief of Rheumatology in the Department of Medicine.

Pulmonary —including idiopathic and scleroderma-associated pulmonary fibrosis—is a fatal disease marked by scarring and hardening of lung tissue. The cause is often unknown, and there is currently no effective treatment.

Previously, it was generally accepted in the field that were unimportant to the development of pulmonary fibrosis. But data from Northwestern's extensive research program in scleroderma—an autoimmune disease closely tied to pulmonary fibrosis that results in hardening of the skin—suggested immune may actually play an important role.

To test that hypothesis, the team of scientists utilized next-generation sequencing technologies and novel animal models generated at Northwestern to trace immune cells throughout the progression of pulmonary fibrosis.

They also applied those tools to the analysis of tissue samples collected at Northwestern Medicine hospitals, correlating the animal model data with the patient samples. "One of the strengths of our study is that we go from bench to bedside," Perlman said.

The scientists discovered that a new sub-population of immune cells called monocyte-derived alveolar macrophages were in fact a key driver of disease development in pulmonary fibrosis. Further, the genetic deletion of this population of cells prevented fibrosis in mouse models.

"This will be transformative for the field," said first author Alexander Misharin, MD, PhD, assistant professor of Medicine in the Division of Pulmonary and Critical Care. "Pulmonary fibrosis is a complex disease—it's not driven by a single gene or cell type—but this study now demonstrates that these immune cells play a key role. This will change the current paradigm."

The findings have important implications for the development of future therapies, especially given that targeting such cells may lead to fewer adverse effects. "These cells are attractive for therapy because they don't need to be there. They aren't necessary for normal function or developmental purposes," said Perlman, also the Mabel Greene Myers Professor of Medicine.

The new methods used in the research could also spark future research in the field.

"This is a novel application of genomic technologies to understanding pulmonary fibrosis," said Budinger, also the Ernest S. Bazley Professor of Airway Diseases and a professor of Cell and Molecular Biology. "By showing that these technologies can be directly applied to patient samples, we offer the promise of incorporating them into personalized medicine approaches. It creates a resource for the research community to develop novel therapies."

The team is now actively deploying these technologies to examine lungs from patients with pulmonary fibrosis, fibrotic skins from patients with scleroderma and joints from patients with rheumatoid arthritis to identify other common immune mechanisms in fibrosis that might be targets for new therapies.

Budinger, Perlman and Misharin are also members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

In a separate finding, the scientists discovered that injury to a mouse early in life permanently altered the immune cell population in the lungs, findings that could have implications for aging research. "Severe injury early in life permanently changes you, in a way that might impact your susceptibility to disease when you get older," Budinger said.

Explore further: Vaccine improves fibrosis in mouse model of idiopathic pulmonary fibrosis

More information: Alexander V. Misharin et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span, The Journal of Experimental Medicine (2017). DOI: 10.1084/jem.20162152

Related Stories

Vaccine improves fibrosis in mouse model of idiopathic pulmonary fibrosis

April 7, 2016
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease characterized by lung fibrosis and declining lung function. There are currently few effective treatments for IPF, and the median survival following diagnosis ...

Mast cells have critical role in initializing pulmonary fibrosis

April 11, 2013
Pulmonary fibrosis is a chronic, deadly disease that affects five million people worldwide. It is irreversible, its cause is poorly understood, and it has a median survival of only about 3 years. A new study that implicates ...

Study finds cause of pulmonary fibrosis in failure of stem cells that repair lungs

November 22, 2016
Cedars-Sinai investigators have pinpointed a major cause of pulmonary fibrosis, a mysterious and deadly disease that scars the lungs and obstructs breathing. The disease, which has no known cure, appears to result from the ...

Study finds key regulator in pulmonary fibrosis

October 20, 2016
A Yale-led research team has identified an important enzyme that could lead to new therapies for a chronic fatal lung disease that affects hundreds of thousands in the United States each year.

Mitophagy in macrophages is a key step toward pulmonary fibrosis

February 24, 2016
Idiopathic pulmonary fibrosis is a devastating disease, and recently approved therapies have limited efficacy. Lungs become damaged with fibrotic scarring, and the median length of survival after diagnosis is three to five ...

Researchers discover link between aging, devastating lung disease

February 23, 2017
A Mayo Clinic study has shown evidence linking the biology of aging with idiopathic pulmonary fibrosis, a disease that impairs lung function and causes shortness of breath, fatigue, declining quality of life, and, ultimately, ...

Recommended for you

Mind-body therapies immediately reduce unmanageable pain in hospital patients

July 25, 2017
Mindfulness training and hypnotic suggestion significantly reduced acute pain experienced by hospital patients, according to a new study published in the Journal of General Internal Medicine.

Researchers report new system to study chronic hepatitis B

July 25, 2017
Scientists from Princeton University's Department of Molecular Biology have successfully tested a cell-culture system that will allow researchers to perform laboratory-based studies of long-term hepatitis B virus (HBV) infections. ...

Research examines lung cell turnover as risk factor and target for treatment of influenza pneumonia

July 24, 2017
Influenza is a recurring global health threat that, according to the World Health Organization, is responsible for as many as 500,000 deaths every year, most due to influenza pneumonia, or viral pneumonia. Infection with ...

Scientists propose novel therapy to lessen risk of obesity-linked disease

July 24, 2017
With obesity related illnesses a global pandemic, researchers propose in the Journal of Clinical Investigation using a blood thinner to target molecular drivers of chronic metabolic inflammation in people eating high-fat ...

Raccoon roundworm—a hidden human parasite?

July 24, 2017
The raccoon that topples your trashcan and pillages your garden may leave more than just a mess. More likely than not, it also contaminates your yard with parasites—most notably, raccoon roundworms (Baylisascaris procyonis).

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.