Abstract
Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury after viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and SARS coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell prorepair function after lung injury remains unknown. Here, we showed that aging results in a cell-autonomous impairment of reparative Treg cell function after experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provided 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. Strategies to restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia.
| Original language | English (US) |
|---|---|
| Article number | e141690 |
| Journal | JCI Insight |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 22 2021 |
Funding
We thank the Northwestern University Flow Cytometry Core Facility supported by a Cancer Center Support Grant (CCSG) (NCI CA060553). Flow cytometry cell sorting was performed using BD Biosciences FACSAria SORP systems purchased through the support of NIH grants 1S10OD011996-01 and 1S10OD026815-01. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by NIH grant P30CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Imaging work was performed at the Northwestern University Center for Advanced Microscopy supported by NCI CCSG P30CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. We also wish to thank the Northwestern University RNA-Sequencing Center/Genomics Lab of the Pulmonary and Critical Care Medicine and Rheumatology Divisions. This research was supported in part through the computational resources and staff contributions provided by the Genomics Compute Cluster, which is jointly supported by the Feinberg School of Medicine, the Center for Genetic Medicine, and Feinberg’s Department of Biochemistry and Molecular Genetics, the Office of the Provost, the Office for Research, and Northwestern Information Technology. The Genomics Compute Cluster is part of Quest, Northwestern University’s high-performance computing facility, with the purpose to advance research in genomics. LMN was supported by NIH awards T32HL076139 and F32HL151127. MATA was supported by NIH award T32GM008152. BDS was supported by NIH awards K08HL128867, U19AI135964, P01AG049665, and R01HL149883 and the Eleanor Wood Prince Grant of the Woman’s Board of Northwestern Memorial Hospital.
ASJC Scopus subject areas
- General Medicine
