Epithelial-mesenchymal transition: potential role in obliterative bronchiolitis?
- 1Heart and Lung Institute, St Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA
- 2Department of Pediatrics, University of Arizona, Tucson, Arizona, USA
- 3Division of Pulmonary and Critical Care Medicine, Will Rogers Institute Pulmonary Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Correspondence to Dr B C Willis, Heart and Lung Institute, 500 Thomas Rd, Suite 500, St Joseph’s Hospital and Medical Center, Phoenix, AZ 85260, USA; brigham.willis{at}chw.edu
Lung transplantation remains the only viable option for many patients suffering from a variety of progressive or intractable end-stage lung diseases. Despite significant advances in the prevention of early graft rejection, ischaemia-reperfusion injury and acute management of lung transplant recipients, significant challenges remain in the chronic management of patients after lung transplantation.1 In this issue of Thorax, Borthwick and colleagues2 provide intriguing new evidence that implicates the airway epithelium directly in the pathogenesis of bronchiolitis obliterans syndrome (BOS), the most significant factor in determining long-term lung graft survival (see page 770). As discussed in the study, the pathological lesion of BOS is obliterative bronchiolitis (OB), which recently has been postulated to be at least partially a disease of aberrant epithelial repair processes.3 Borthwick and colleagues provide evidence that epithelial to mesenchymal transition (EMT), a process whereby epithelial cells undergo a complete lineage transition to become fibroblasts and/or myofibroblasts, may underlie the dysfunctional airway repair processes that lead to OB. This study, and others like it, attempt to redefine traditional paradigms regarding normal airway epithelial biology and disease pathogenesis, and have the potential to lead to entirely new therapeutic avenues for previously untreatable disease processes such as BOS.
OB is characterised by initial inflammation of the small airways followed by airway remodelling, aberrant epithelial regeneration and repair, proliferation of fibroblasts and myofibroblasts, deposition of extracellular matrix (ECM) and eventual airway obstruction.4 The initial inflammatory response is the result of an allogeneic immune response initiated against donor antigens in the graft endothelial and airway epithelial cells. This response characteristically generates antigen-specific graft-infiltrating destructive lymphocytes. The lymphocytes facilitate activation of macrophages and a variety of other inflammatory cells, with resultant …
