Role of NK cells in circadian regulation of lung inflammation

Abstract Circadian rhythms form an anticipatory system wherein various aspects of cellular physiology oscillate across a 24hrs period; these have been known to modulate facets immunity. We previously shown that mice infected with Influenza A virus (IAV) at dusk had 3-fold higher mortality than littermates dawn--a hallmark circadian regulation. This time-of-day specific protection was lost when NK cells were depleted just before the infection, suggesting role in mediating regulation IAV infection. investigated mechanism underlying cells, both cell-intrinsic or extrinsic lung injury. noted viral clearance unaffected, but immunopathology markedly worse controls. Next, we effect loss clock on cell behavior and found splenic pulmonary naïve disrupted less mature phenotype control intact clock. Our transcriptomic profiling sorted from clock-intact versus clock-disrupted animals revealed several genes regulate cycle progression functional maturity differentially expressed two groups. Pulmonary mutant mice. Finally, Ncr1cre+Bmal1fl/flmice (core gene Bmal1deleted cells) through heightened not delayed clearance. In summary, data show cell-autonomous boost host tolerance mediate Supported by grants NIH (R01HL155934-01A1, R01HL147472, R01AI137062-01)