The role of circulating epithelial cells (CECs) in autoimmune-mediated fibrotic diseases, such as Scleroderma

Description

Funder: The Kennedy Trust

The precise processes that initiate fibrotic diseases such as Systemic Sclerosis (SSc) remains largely unknown. Aberrant regulation of normal tissue repair processes including deregulation of the immune system are key features in the blood, skin and lungs of SSc patients. Tissue repair relies on sophisticated, tightly controlled cellular and molecular processes, triggered by any type of tissue damage from injury to cell death. Recently, it has been identified that the process of metastasis – how cancer cells spread throughout the body- is in fact a naturally occurring process that is corrupted by cancer and contributes to normal tissue repair. Using a variety of cancer models, we have identified that normal, non-cancerous epithelial stem cells circulate in the blood like metastatic cancer cells, and contribute to tissue repair or, when in excess, caused generalized tissue inflammation and fibrosis. Beyond the major implication in cancer research, the study has the potential to open a completely new venue for research in immune-driven fibrosis. Here, we aim to: a) Characterize the immune responses to Circulating Epithelial Cells (CECs) in the mouse model that led to the discovery of their profibrotic effect and; b) Characterize CECs in patients with SSc to determine whether they may play a direct role in the disease process. The results of the studies we propose in this application have the potential to spark two new fields of investigation including 1. A new link between cancer and immunity that could lead to targeted immune-based prevention of cancer metastasis and 2. The role of CECs as a new mechanism and potential target of the autoimmune activation observed in Systemic Sclerosis.