Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.
Marcela Helena Gonçalves PereiraLuciana SantiagoCecilia Gómez RavettiPaula Frizera VassalloMarcus Vinicius Melo de AndradeMariana Sousa VieiraFernanda de Fátima Souza de OliveiraNatália Virtude CarobinGuangzhao LiAdriano de Paula SabinoVandack NobreHelton da Costa SantiagoPublished in: Immunology (2022)
Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.
Keyphrases
- regulatory t cells
- sars cov
- mechanical ventilation
- intensive care unit
- coronavirus disease
- peripheral blood
- dendritic cells
- induced apoptosis
- end stage renal disease
- young adults
- cell cycle arrest
- respiratory syndrome coronavirus
- pulmonary hypertension
- acute respiratory distress syndrome
- chronic kidney disease
- poor prognosis
- early onset
- emergency department
- ejection fraction
- signaling pathway
- rheumatoid arthritis
- cell therapy
- immune response
- cell death
- single cell
- prognostic factors
- endoplasmic reticulum stress
- cardiac arrest
- peritoneal dialysis
- transcription factor
- stem cells
- oxidative stress
- extracorporeal membrane oxygenation
- respiratory failure
- patient reported outcomes