Scientists discover new cellular process leading to lung fibrosis

January 15, 2014, Trinity College Dublin

Scientists in Trinity College Dublin have identified a new process that causes scarring in the lungs of patients with idiopathic pulmonary fibrosis (IPF). The research was led by Professor Padraic Fallon, School of Medicine, Trinity College Dublin and was an international collaboration with scientists from University College Dublin, MRC-LMB Cambridge, the University of Edinburgh, and the University of Erlangen. The study was published in the Proceedings of the National Academy of Sciences.

Pulmonary fibrosis arises as a result of excessive scarring (fibrosis) of the tissue and is associated with shortness of breath.  IPF is a progressive chronic condition for which there are very few effective therapies available and consequentially there is a poor prognosis.  Despite extensive investigation, the causes underlying IPF remain unknown although it has been linked with exposure to cigarette smoke and other environmental factors such as occupational exposure to gases, chemicals and dust.  It is hypothesized that chronic and repeated injury to lung cells, in particular alveolar epithelial cells, results in the release of pro-fibrotic factors such as transforming growth factor β (TGF β). These factors induce fibroblasts to release collagen that leads to scaring of the lungs tissue and thereby compromising the function of the lungs.

In this new study the authors have used animal models of to show an increase in expression of a cytokine, interleukin-25 (IL-25), in the lungs with the development of pulmonary fibrosis being dependent on the presence of IL-25. In addition, a new role for a novel immune cell type, the type 2 innate lymphoid cell (ILC2) previously discovered by Professor Fallon and colleagues, in the initiation of fibrosis was described. It was also shown that the ILC2, induced by IL-25, cells themselves can induce collagen deposition in the lung via the release of pro-fibrotic factors such as IL-13.

To address the relevance of these findings to human disease a cohort of patients with were recruited from clinical collaborators Professor Seamas Donnelly (St Vincent's Hospital and University College Dublin), Dr Nikhil Hirani (University of Edinburgh) and Dr Ruairi Fahy (St James's Hospital).  Lung biopsies samples were recovered from patients at initial diagnosis and on follow-up visits to assess progression. High levels of IL-25 in the lungs of patients at initial IPF diagnosed were associated with disease progression.  Furthermore, a population of ILC2 was also present in the lungs of IPF patients but not control patients. 

These discoveries open up a new perspective on how scarring develops in the lungs of people, as well as in other sites of the body, and further identifies potential avenues to develop therapies.

Professor Padraic Fallon, Science Foundation Ireland Stokes Professor of Translation Immunology who led the study commented: "We have highlighted in laboratory models and in patients how the immune system can malfunction to stimulate specific cytokines and novel cell types that can lead to tissue damage which, in the context of this study, can induce lung fibrosis. We are now addressing how we can reverse such tissue scarring and identify why there are differences in severity of pulmonary inflammation and fibrosis between patients with lung diseases, such as IPF and asthma."

Professor Mark Ferguson, Director General, Science Foundation Ireland which funded the research jointly with the National Children's Research Centre, and Chief Scientific Adviser to the Government of Ireland commented: "Pulmonary fibrosis is a devastating condition, with few treatment options. Professor Fallon's research results provide a new understanding of the disease process and suggest new targets for future potential therapies – an example of excellent scientific research with potential future health and economic impacts."

These studies may have broader implications to human disease. Professor Fallon and Wellcome Trust funded scientist Dr Sean Saunders in collaboration with Professor Graham Ogg (University of Oxford, UK) and Dr Andrew McKenzie (LMB Cambridge, UK) also just published this month in the leading medical peer-review journal The Journal of Experimental Medicine studies that implicate ILC2 and IL-25 in the development of atopic dermatitis (eczema) in patients.  The first author of the Proceedings of the National Academy of Sciences paper Dr Emily Hams from Trinity College Dublin has also recently implicated a function for these cellular responses in regulation of obesity. These new studies raise the potential for therapies targeting the initial responses that evoke aberrant inflammation that leads to a range of major human inflammatory diseases.

Explore further: Personalising treatment in idiopathic pulmonary fibrosis

More information: Emily Hams, Michelle E. Armstrong, Jillian L. Barlow, Sean P. Saunders, Christian Schwartz, Gordon Cooke, Ruairi J. Fahy, Thomas B. Crotty, Nikhil Hirani, Robin J. Flynn, David Voehringer, Andrew N. J. McKenzie, Seamas C. Donnelly, and Padraic G. Fallon. "IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis." PNAS 2013 ; published ahead of print December 16, 2013, DOI: 10.1073/pnas.1315854111

Related Stories

Personalising treatment in idiopathic pulmonary fibrosis

December 19, 2013
Researchers in UCD Conway Institute have identified a potential biomarker of rapidly progressive pulmonary fibrosis and pinpointed a defective molecular function as a potential therapeutic target.

Newly identified biomarkers help predict outcome in idiopathic pulmonary fibrosis

October 2, 2013
A Yale-led study has identified a gene expression profile that can predict outcomes and lead to better treatment for one of the most lethal lung diseases, idiopathic pulmonary fibrosis (IPF). The study appears in Science ...

Finding cellular causes of lung-hardening disease

September 17, 2013
(Medical Xpress)—Idiopathic Pulmonary Fibrosis, or IPF, is an incurable lung disease that, over time, turns healthy lung tissue into inflexible scar tissue – hardening the lungs and eventually causing respiratory distress ...

Study reveals much-needed strategy to protect against deadly liver fibrosis

August 15, 2013
Chronic liver disease is a leading cause of death in the United States, in part because it often causes the formation of harmful scar tissue—a process known as fibrosis. A study published by Cell Press August 15 in the ...

RCSI research breakthrough in understanding hereditary emphysema

January 13, 2014
Researchers from the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital have made an important breakthrough in the understanding and treatment of hereditary emphysema.  Their research findings were published ...

Recommended for you

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

Zika virus damages placenta, which may explain malformed babies

January 18, 2018
Though the Zika virus is widely known for a recent outbreak that caused children to be born with microencephaly, or having a small head, and other malformations, scientists have struggled to explain how the virus affects ...

Certain flu virus mutations may compensate for fitness costs of other mutations

January 18, 2018
Seasonal flu viruses continually undergo mutations that help them evade the human immune system, but some of these mutations can reduce a virus's potency. According to new research published in PLOS Pathogens, certain mutations ...

Study reveals how MRSA infection compromises lymphatic function

January 17, 2018
Infections of the skin or other soft tissues with the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. ...

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.