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

Luisa Morales-Nebreda, Kathryn A. Helmin, Nikolay S. Markov, Raul Piseaux, Manuel A. Torres Acosta, Hiam Abdala-Valencia, Yuliya Politanska, View ORCID ProfileBenjamin D. Singer
doi: https://doi.org/10.1101/2020.06.05.135194
Luisa Morales-Nebreda
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Kathryn A. Helmin
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Nikolay S. Markov
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Raul Piseaux
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Manuel A. Torres Acosta
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Hiam Abdala-Valencia
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Yuliya Politanska
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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Benjamin D. Singer
1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
2Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
3Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
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  • ORCID record for Benjamin D. Singer
  • For correspondence: benjamin-singer@northwestern.edu
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Abstract

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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 05, 2020.
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Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia
Luisa Morales-Nebreda, Kathryn A. Helmin, Nikolay S. Markov, Raul Piseaux, Manuel A. Torres Acosta, Hiam Abdala-Valencia, Yuliya Politanska, Benjamin D. Singer
bioRxiv 2020.06.05.135194; doi: https://doi.org/10.1101/2020.06.05.135194
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Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia
Luisa Morales-Nebreda, Kathryn A. Helmin, Nikolay S. Markov, Raul Piseaux, Manuel A. Torres Acosta, Hiam Abdala-Valencia, Yuliya Politanska, Benjamin D. Singer
bioRxiv 2020.06.05.135194; doi: https://doi.org/10.1101/2020.06.05.135194

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