Idiopathic pulmonary fibrosis (IPF) is a progressive and intractable disease with a poor long-term prognosis. My PhD project aims to understand the signals that lead to IPF, and how these could be better controlled.

IPF is caused by lung scarring (fibrosis), resulting in reduced lung function. The aetiology of IPF is still unknown, although immune responses to risk factors such as tobacco smoke, metal and wood dust, and gastroesophageal reflux have been implicated.

In allergic lung conditions such as asthma, an allergic immune response causes the damage of epithelial cells lining the airways, inflammation, and tissue repair within the lung. However, in IPF, similar types of immune responses appear to cause an aberrant healing of tissues.

The lung tissue communicates with the immune system through the release of "messenger" molecules, known also as cytokines, following injury to the epithelium of the lung. Epithelial cytokines with particular importance in asthma are IL-25, IL-33, and TSLP. These molecules induce allergic asthma, and clinical trials are underway to block these molecules to attempt to reduce disease. However, recent evidence indicates that IL-25, IL-33, and TSLP work synergistically, and that full suppression of immune responses only occurs when all three of these molecules are blocked simultaneously. Therefore it has been hypothesised that that the same is true in fibrosis.

Parasitic worms are particularly good at suppressing allergic immune responses, allowing them to survive in their hosts. The McSorley lab has shown that parasitic worms can suppress these epithelial cytokine responses (especially IL-33) through uniquely effective pathways, avoiding tissue scarring. Therefore, I will use parasite products and/or blocking proteins to suppress IL-25, IL-33 and TSLP, to treat IPF.