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Low TET1 Expression Levels in COPD Are Associated with Airway and Blood Neutrophilia

Ji, H.; Zhang, X.; Linderholm, A.; Harper, R. W.; Juarez, M. M.; Schivo, M.; Kuhn, B. T.; Zeki, A. A.; Haczku, A.

2025-04-16 respiratory medicine
10.1101/2025.04.15.25325889 medRxiv
Show abstract

Epigenetic dysregulation, particularly DNA methylation variations, is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Ten-eleven translocation (TET) proteins (TET1, TET2, and TET3) regulate DNA methylation and gene transcription. Impaired TET1 expression was previously associated with airway inflammation and asthma. Here we investigated TET gene associations with COPD severity. We found that reduced TET1 expression in peripheral blood mononuclear cells was associated with higher sputum and blood neutrophil counts, decreased lung function and increased disease severity in patients. These findings support a potential protective role and warrant further mechanistic investigations into the actions of TET1 in COPD.

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