IFITM1 is required for epithelial mesenchymal transition in airway remodeling of allergic asthma.

BACKGROUND: Interferon-induced transmembrane protein 1 (IFITM1) restricts virus infection. IFITM proteins are involved in Th2 cell differentiation in allergic asthma. The epithelial‒mesenchymal transition (EMT) regulates allergic airway remodeling. We sought to explore the functional contributions and underlying mechanisms of IFITM1 in the EMT associated with allergic asthma. METHODS: The expression of IFITM1 was measured in pulmonary tissues from asthma patients and in a house dust mite (HDM)-induced murine asthma model. The mechanisms by which IFITM1 affects the EMT of airway remodeling were investigated in vitro and in vivo via the use of an IFNAR neutralizing antibody or Ifitm1 knockdown. RESULTS: We demonstrated that airway IFITM1 was increased in patients with asthma. As expected, HDM exposure increased airway IFITM1 in an asthmatic murine model. The increase in IFITM1 was mediated through IFN-β stimulation and subsequent STAT1 signaling activation. Blocking IFNAR or knocking down Ifitm1 mitigated HDM-induced EMT and airway remodeling. Mechanistically, HDM exposure increased IFITM1 and TNC levels in airway epithelial cells, which promoted Th17 cell differentiation and IL-17A production. CONCLUSION: IFIMT1, which is upregulated in airway epithelial cells via the IFN-β and STAT1 signaling pathways, contributes to EMT during allergic airway remodeling and may serve as a potential treatment target for allergic asthma.