CD39(+) Regulatory T Cells Attenuate Lipopolysaccharide-Induced Acute Lung Injury via Autophagy and the ERK/FOS Pathway.
CD39(+) Regulatory T Cells Attenuate Lipopolysaccharide-Induced Acute Lung Injury via Autophagy and the ERK/FOS Pathway.
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DOI：
10.3389/fimmu.2020.602605
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发表时间：
2020
影响因子：
7.3
通讯作者：
Song Y
中科院分区：
文献类型：
--
作者：
Chen C;Li X;Li C;Jin J;Wang D;Zhao Y;Gu Y;Chen M;Zhu S;Liu H;Lv T;Zhang F;Song Y
急性呼吸窘迫综合征（ARDS）的特征是不可控制的细胞因子风暴，由于缺乏有效的治疗，这与高死亡率有关。调节性T细胞（Regulatory T cells，TCRs）在维持免疫稳态中起着不可或缺的作用，CD 39被认为是TCRs的功能性细胞标志物。本研究旨在探讨CD 39 + T细胞亚群在急性肺损伤（acute lung injury，ALI）中的作用，并探讨CD 39 + T细胞亚群在ARDS患者中的表达情况。我们发现，脂多糖（LPS）治疗后，CD 39 −/−小鼠表现出更严重的炎症，野生型（WT）小鼠表现出外周血中CD 39 + T细胞的频率降低。此外，CD 39 + T细胞在体外对LPS诱导的炎症具有保护作用，并且过继转移CD 39 + T细胞在体内对ALI具有治疗作用。我们进一步探索了影响TcB上CD 39表达的机制。LPS诱导的肺部炎症通过自噬介导的CD 39下调损害了TclO的免疫抑制作用。此外，CD 39通过激活ERK 1/2-FOS通路诱导TCFs自身的表达。与这一发现相一致，ARDS患者外周血中CD 39 + Tregs的频率也降低，并且与疾病严重程度正相关。本研究结果提示，过继转移CD 39 + T细胞可能为临床防治ARDS提供一种新的方法。
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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影响因子：
8.8
作者：
Parekh D;Dancer RCA;Scott A;D'Souza VK;Howells PA;Mahida RY;Tang JCY;Cooper MS;Fraser WD;Tan L;Gao F;Martineau AR;Tucker O;Perkins GD;Thickett DR
通讯作者：
Thickett DR
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
81.5
作者：
Matthay, Michael A.;Zemans, Rachel L.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.
影响因子：
4.8
作者：
Gerner, Marlene C.;Ziegler, Liesa S.;Schmetterer, Klaus G.
通讯作者：
Schmetterer, Klaus G.