E26 transformation-specific-1 controls asthma development by regulating the CD4+ Th2/Th17 immune response involved transcription factors in active genomic transcriptional regions

Abstract Asthma is a chronic respiratory disease characterized by airway inflammation and immune cell imbalance. The transcription factor E26 transformation-specific-1 regulates immune cell functions, but its role in asthma remains unclear. Here, we generated Ets1 heterozygous (Ets1+/−) mice by constitutively knocking out exons 7 and 8 of Ets1, confirmed significantly reduced Ets1 expression via western blot. Asthma models were then established in both wild-type and Ets1+/− mice, revealing more severe pulmonary inflammation in Ets1+/− mice. Then, we systematically explored the regulatory effects of Ets1 on immune cells function and inflammatory responses in asthma. Further analyses showed enhanced CD4+ helper T (Th) 2/Th17 cell responses and elevated interleukin-4 and interleukin-17A secretion in the asthma Ets1+/− mice. By combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we identified 17 transcription factors regulated by Ets1 and linked to the function of mitotic processes in asthma. These findings suggest that Ets1 mitigates asthma by modulating CD4+ Th2/Th17 immune responses and regulating transcription factors associated with cell cycle processes.