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...
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Veröffentlicht in: | Frontiers in immunology 2021-01, Vol.11, p.602605 |
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Sprache: | eng |
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Zusammenfassung: | 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
and the adoptive transfer of CD39
Tregs had a therapeutic effect on ALI
. 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
the autophagy-mediated downregulation of CD39. In addition, CD39 induced the expression of itself in Tregs
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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ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2020.602605 |