Telomere shortening in type II pneumocytes relates to idiopathic pulmonary fibrosis

Background: Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease with a median post-diagnostic survival of approximately 4 years. Recently it has been discovered that telomere length (TL) maintenance plays a key role in IPF. In patients with different types of pulmonary fibrosis, shortening of leukocyte telomere length was found, especially in telomerase mutation-related disease. In this pilot study, we measured TL in the regenerating cells of lung alveoli, so-called type II pneumocytes. These cells are considered to be the crucial cell type in IPF pathogenesis. Methods: Tissue slides of sporadic IPF patients and controls were stained using telomere Fluorescence In Situ Hybridization (FISH). Type II cells were identified using the proSPC antibody from Merck Millipore (ab3786, Rabbit 1:300). Subsequently, quantification of telomere fluorescence was measured per cell type, discriminating between type II and all the surrounding cells combined. These were classified as non-type II cells. Results: Type II pneumocyte TL was significantly shorter in fibrotic areas compared to non-fibrotic areas or control tissue (p-values of 0.004 and 0.0023 respectively). In non-type II pneumocytes TL did not differ between fibrotic and non-fibrotic areas. Furthermore, within controls no differences were observed between type II cells and non-type II cells. Conclusion: In conclusion, the co-localization of short telomeres in type II cells and the pathophysiology of IPF suggests that telomere shortening plays a critical role in the fibrotic remodeling of lung tissue in this disease.