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TET1 Protects the Lungs from Diesel Exhaust Particle-Induced Inflammation and Abnormal Function
Stephanie N Henson1, Anthony P Brown1, Sweeney P Elston1
1University of California, Davis.
Research Square
|June 29, 2026
Summary
The DNA demethylation enzyme TET1 plays a crucial role in regulating airway responses to diesel exhaust particles (DEP). Loss of TET1 exacerbates inflammation and airway hyperresponsiveness, suggesting TET1-dependent pathways as a therapeutic target for pollution-induced asthma.
Area of Science:
- Environmental Health
- Epigenetics
- Pulmonology
Background:
- Diesel exhaust particles (DEP) are a significant cause of asthma exacerbations, linked to oxidative stress and inflammation.
- Epigenetic mechanisms, particularly DNA demethylation, are implicated in environmental lung diseases.
- The specific role of TET1 (ten-eleven translocation 1) in DEP-induced airway dysfunction is not well understood.
Purpose of the Study:
- To investigate the contribution of TET1 to epithelial and airway responses to DEP exposure.
- To elucidate the mechanisms by which TET1 influences inflammatory and detoxification pathways in the airways.
Main Methods:
- Silencing TET1 in human bronchial epithelial cells (HBECs) followed by DEP exposure to assess transcriptomic and cytokine changes.
- Utilizing Tet1 heterozygous (Tet1+/-) mice exposed to DEP to evaluate airway hyperresponsiveness, inflammation, and immune responses.
- Employing interventions targeting TET activity, aryl hydrocarbon receptor (AhR) signaling, and oxidative stress.
Main Results:
- TET1 deficiency amplified DEP-induced pro-inflammatory responses and suppressed detoxification genes in HBECs.
- Tet1+/- mice showed increased airway hyperresponsiveness, neutrophilic inflammation, and elevated Th17-associated cytokines after DEP exposure.
- Inhibition of AhR signaling and reduction of oxidative stress partially attenuated DEP-induced inflammation and hyperresponsiveness.
Conclusions:
- TET1 acts as a key epigenetic regulator integrating detoxification and inflammatory pathways in airway epithelium during environmental exposures.
- Modulating TET1-dependent pathways offers a potential therapeutic strategy to mitigate susceptibility to pollution-induced airway diseases like asthma.
- These findings highlight the critical role of TET1 in mediating airway epithelial responses to environmental pollutants.
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