BACKGROUND: Transposable elements (TEs) are repetitive sequences of viral origin 
that compose almost half of the human genome. These elements are tightly 
controlled within cells, and if activated, they can cause changes in both gene 
regulation and immune viral responses that have been associated with several 
chronic inflammatory diseases in humans. As oxidants are potent activators of 
TEs, and because oxidative injury is a major risk factor in relation to 
idiopathic pulmonary fibrosis (IPF), we hypothesized that TEs might be involved 
in the regulation of gene expression and so contribute to inflammation in cases 
of IPF. IPF is a fatal lung disease that involves the gradual replacement of the 
alveolar tissue with fibrotic scars as well as the accumulation of inflammatory 
cells in the lower respiratory tract. Although IPF is known to occur as a result 
of the complex interaction between age, environmental risk factors (i.e., 
oxidative stress) and genetics, the relative contributions of these factors to 
the disease remain unclear. To determine whether TEs are associated with IPF, we 
compared the transcriptional profiles of the genes and TEs of lung cells 
obtained from both healthy donors and IPF patients.
RESULTS: We quantified TE and gene expression levels using a published bulk 
RNA-seq dataset containing 24 subjects (16 donors and eight IPF patients), 
including three lung-cell types per subject, as well as an scRNA-seq dataset 
concerning 16 subjects (eight donors and eight IPF patients). We found evidence 
of TE dysregulation in the alveolar type II lung cells and alveolar macrophages 
of the IPF patients. In addition, the activation of the LINE1 family of elements 
in IPF is associated with the increased expression of TE cellular regulators 
(MOV10, IFI16, SAMHD1, and APOBECG3), interferon-stimulating genes (ISG15, IFI6, 
IFI27, IFI44, and OAS1), chemokines (CX3CL1 and CXCL9), and interleukins 
(IL15RA). We also propose that TE derepression might be involved in the 
regulation of previously reported IPF candidate genes (MUC5B, CHL1, SPP1, and 
MMP7).
CONCLUSION: Based on our findings, we propose that TE derepression plays an 
important role in the regulation of gene expression and can also prompt both the 
recruitment of inflammatory processes and the disruption of the immunological 
balance, which can lead to chronic inflammation in IPF.