| First Author | Warren R | Year | 2022 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 322 |
| Issue | 4 | Pages | L581-L592 |
| PubMed ID | 35196880 | Mgi Jnum | J:353707 |
| Mgi Id | MGI:7257884 | Doi | 10.1152/ajplung.00378.2021 |
| Citation | Warren R, et al. (2022) Ataxia telangiectasia mutated is required for efficient proximal airway epithelial cell regeneration following influenza A virus infection. Am J Physiol Lung Cell Mol Physiol |
| abstractText | Children and young adults with mutant forms of ataxia telangiectasia mutated (ATM), a kinase involved in DNA damage signaling and mitochondrial homeostasis, suffer from recurrent respiratory infections, immune deficiencies, and obstructive airways disease associated with disorganized airway epithelium. We previously showed in mice how Atm was required to mount a protective immune memory response to influenza A virus (IAV; HKx31, H3N2). Here, Atm wildtype (WT) and knockout (Atm-null) mice are used to investigate how Atm is required to regenerate the injured airway epithelium following IAV infection. When compared to WT mice, naive Atm-null mice had increased airway resistance and reduced lung compliance that worsened during infection before returning to naive levels by 56 days post infection (dpi). Although Atm-null lungs appeared pathologically normal prior to infection by histology, they developed an abnormal proximal airway epithelium after infection that contained E-cadherin+, Sox2+, and Cyp2f2+ cells lacking Scgb1a1 protein expression. Patchy and low expression of Scgb1a1 was eventually observed by 56 dpi. Genetic lineage tracing in HKx31-infected mice revealed Club cells require Atm to rapidly and efficiently restore Scgb1a1 expression in proximal airways. Since Scgb1a1 is an immunomodulatory protein that protects the lung against a multitude of respiratory challenges, failure to efficiently restore its expression may contribute to the respiratory diseases seen in A-T individuals. |
