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CD39(+) Regulatory T Cells Attenuate Lipopolysaccharide-Induced Acute Lung Injury via Autophagy and the ERK/FOS Pathway
Acute respiratory distress syndrome (ARDS) is characterized by an uncontrollable cytokine storm, which is associated with high mortality due to lack of effective treatment. Regulatory T cells (Tregs) play an indispensable role in maintaining immune homeostasis and CD39 is considered as a functional...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819860/ https://www.ncbi.nlm.nih.gov/pubmed/33488601 http://dx.doi.org/10.3389/fimmu.2020.602605 |
Sumario: | Acute respiratory distress syndrome (ARDS) is characterized by an uncontrollable cytokine storm, which is associated with high mortality due to lack of effective treatment. Regulatory T cells (Tregs) play an indispensable role in maintaining immune homeostasis and CD39 is considered as a functional cell marker of Tregs. In this study, we aimed to evaluate the effect of CD39(+) Tregs on acute lung injury (ALI) and investigate the frequency of CD39(+) Tregs in ARDS patients. We found that after lipopolysaccharide (LPS) treatment, CD39(−/−) mice exhibited more severe inflammation and wild type (WT) mice exhibited a decreased frequency of CD39(+) Tregs in the peripheral blood. Furthermore, CD39(+) Tregs had a protective effect on LPS-induced inflammation in vitro and the adoptive transfer of CD39(+) Tregs had a therapeutic effect on ALI in vivo. We further sought to explore the mechanisms that affect CD39 expression on Tregs. LPS-induced inflammation in the lung impaired the immunosuppressive effect of Tregs via the autophagy-mediated downregulation of CD39. In addition, CD39 induced the expression of itself in Tregs via activating the ERK1/2-FOS pathway. Consistent with this finding, the frequency of CD39(+) Tregs was also decreased in the peripheral blood of ARDS patients and was positively correlated with disease severity. Our results suggested that the adoptive transfer of CD39(+) Tregs may provide a novel method for the clinical prevention and treatment of ARDS. |
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