Northwestern Researchers Find New Link Between Immune Cells and Pulmonary Fibrosis

Northwestern Researchers Find New Link Between Immune Cells and Pulmonary Fibrosis

A specific subpopulation of immune cells — known as monocyte-derived alveolar macrophages — was found to play an essential role in the development of pulmonary fibrosis (PF). This finding not only contributes new knowledge about the underlying mechanism of PF, but also paves the way for potential new approaches to treat this deadly illness.

The data were reported in a study titled, “Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span,” in The Journal of Experimental Medicine.

Until now, immune cells had not been associated with PF development and progression. However, data from a research program on scleroderma — an autoimmune disease characterized by skin thickening that can affect multiple organs — by Chicago’s Northwestern University have changed this paradigm by suggesting that immune cells play an important role in fibrosis.

To test this hypothesis, researchers used next-generation sequencing technologies and mouse models specifically created to allow immune cells to be tracked throughout the progression of PF. Researchers then used these same tools to analyze patient tissue samples collected at Northwestern Medicine hospitals.

With these advanced methods, the team found that a subgroup of immune cells, the monocyte-derived alveolar macrophages, were recruited to the lungs during fibrosis and were essential to fibrosis development. These cells were different from lung resident alveolar macrophages, which were not found to participate in the fibrotic process.

Furthermore, researchers found that by removing these monocyte-derived alveolar macrophages, fibrosis was prevented in animal models.

“This will be transformative for the field,” Alexander Misharin, MD, PhD, assistant professor of medicine at Northwestern Medicine’s Division of Pulmonary and Critical Care and first author of the study, said in a news release. “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.”

By analyzing samples collected from PF patients, the research team confirmed that these cells were also present in human disease.

Based on the results, the team suggested that selectively targeting these specific immune cells could pave the way for new therapies. This targeted strategy could also resolve the issue of adverse effects caused by current treatments that target global immune tissue cell populations.

“One of the strengths of our study is that we go from bench to bedside,” said Harris Perlman, PhD, chief of rheumatology at Northwestern’s Department of Medicine and co-lead author of the study. “These cells are attractive for therapy because they don’t need to be there. They aren’t necessary for normal function or developmental purposes.”

The team is currently using the methodologies to examine lung tissue samples from patients with PF, fibrotic skin samples from patients with scleroderma, and joint samples from patients with rheumatoid arthritis. The goal is to find common mechanisms that could explain the fibrosis process and identify potential therapeutic targets.

“This is a novel application of genomic technologies to understanding pulmonary fibrosis,” said Scott Budinger, MD, chief of pulmonary and critical care at Northwestern Medicine and co-lead author of the study. “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.”

3 comments

  1. Colin Mortlock says:

    Very interesting, but is there any way these cells can be targeted and potentially destroyed to leave the remaining tissue intact?

    • Alice Melão says:

      Dear Colin, The results of this preclinical study are to some extend preliminary. These cells were reported for the first time in this study, so more studies may be needed to fully characterize them. Yet, the results of the study showed that targeting the transformation of monocytes into these alveolar macrophages may be a therapeutic possibility. Will it affect the remaining tissues… only further studies will give us an answer to that.

  2. Sandra Bereza says:

    As a patient with PF and RA, I would be interested in finding out more about this research. I would also like to know if they are recruiting for clinical trials.

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