Evaluating the role of TLR3 L412F in disease progression in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a lung disease of unknown cause which leads to excessive scarring of the lungs, resulting in loss of lung function, respiratory failure and ultimately, death. IPF is believed to be caused by abnormal repair of the lung after a chronic injury by an unknown agent to the lining of the lung (the epithelium), in patients with a specific genetic defect. In many cases, IPF has a worse prognosis than cancer.
Each year, 29 individuals per 100,000 will get IPF. Furthermore, 15% of these patients will develop a very aggressive and rapidly progressive form of IPF and will die approximately 12 after their diagnosis. In contrast, some patients develop a form of IPF that progresses very slowly. One of the greatest difficulties facing clinicians today is the inability to determine at diagnosis which of their patients will develop a very aggressive and fatal form of IPF. Certain viral infections are believed to be associated with initiating the lung damage which causes IPF or making the existing conditions worse.
Prof Seamas Donnelly's research group at Trinity College Dublin has identified an anti-viral receptor called Toll-like receptor 3 (TLR3) which, when defective, is associated with making IPF worse and causing its rapid progression. Specifically, they have identified a genetic mutation in the TLR3 gene (called TLR3 L412F), which when present can make IPF develop very quickly and cause death. In this research project, our aim is to work out how TLR3 L412F causes these dreadful effects and death in IPF patients. In the future, we hope that TLR3 L412F will help clinicians to determine what form of IPF their patients will develop at diagnosis in order to provide these patients with the best clinical treatment and to prevent their early death.

Award Date: 23 October 2015
Award Value: €318,797
Principal Investigator: Professor Seamas Donnelly
Host Institution: Trinity College Dublin
Scheme: Health Research Awards