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Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia

By Luisa Morales-Nebreda, Kathryn A. Helmin, Nikolay S. Markov, Raul Piseaux, Manuel A Torres Acosta, Hiam Abdala-Valencia, Yuliya Politanska, Benjamin D. Singer

Posted 05 Jun 2020
bioRxiv DOI: 10.1101/2020.06.05.135194

Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury following viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell pro-repair function following lung injury remains unknown. Here, we show that aging results in a cell-autonomous impairment of reparative Treg cell function following experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provide insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Novel strategies that restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia. ### Competing Interest Statement BDS has a pending patent application: US Patent App. 15/542,380, Compositions and Methods to Accelerate Resolution of Acute Lung Inflammation. The other authors declare no competing interests.

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