TY - JOUR TI - Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates AU - Issah, Yasmine AU - Naik, Amruta AU - Tang, Soon Y AU - Forrest, Kaitlyn AU - Brooks, Thomas G AU - Lahens, Nicholas AU - Theken, Katherine N AU - Mermigos, Mara AU - Sehgal, Amita AU - Worthen, George S AU - FitzGerald, Garret A AU - Sengupta, Shaon A2 - Davenport, Miles P A2 - McKeating, Jane A VL - 10 PY - 2021 DA - 2021/03/02 SP - e61241 C1 - eLife 2021;10:e61241 DO - 10.7554/eLife.61241 UR - https://doi.org/10.7554/eLife.61241 AB - Adverse early-life exposures have a lasting negative impact on health. Neonatal hyperoxia that is a risk factor for bronchopulmonary dysplasia confers susceptibility to influenza A virus (IAV) infection later in life. Given our previous findings that the circadian clock protects against IAV, we asked if the long-term impact of neonatal hyperoxia vis-à-vis IAV infection includes circadian disruption. Here, we show that neonatal hyperoxia abolishes the clock-mediated time of day protection from IAV in mice, independent of viral burden through host tolerance pathways. We discovered that the lung intrinsic clock (and not the central or immune clocks) mediated this dysregulation. Loss of circadian protein, Bmal1, in alveolar type 2 (AT2) cells recapitulates the increased mortality, loss of temporal gating, and other key features of hyperoxia-exposed animals. Our data suggest a novel role for the circadian clock in AT2 cells in mediating long-term effects of early-life exposures to the lungs. KW - neonatal lung disease KW - circadian rhythm KW - hyperoxia KW - type 2 alveolar cells KW - influenza KW - lung injury JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -