Toward a Better Understanding of Severe Influenza in the Older Patient

Influenza virus infection (the flu), which causes severe damage to the lungs, carries a disproportionate and devastating impact on older patients. Despite decades of intensive research effort, we as critical care physicians currently possess no therapies that directly help heal damaged lungs. Since Northwestern Medicine serves an increasingly older patient population, we need a better understanding of how lung healing occurs and to use that knowledge to create new, effective therapies. The PI of this application established a key role for a chemical modification to DNA in guiding lung healing. This modification, called DNA methylation, controls a specialized white blood cell type—the regulatory T cell—which is known to orchestrate lung healing. Therefore, we propose to use state-of-the-art technologies to measure DNA methylation and its effects on regulatory T cells in the context of both aged mice and older hu¬mans with severe influenza. The data this project generates will 1) inform critical studies of therapies designed to heal damaged lungs and 2) provide a spring¬board for the PI to apply for his first large research grant, an NIH R01.