Lung-resident mesenchymal stem cells regulated the inflammatory responses in innate and adaptive immune cells through HVEM-BTLA pathway during ARDS
Lung-resident mesenchymal stem cells regulated the inflammatory responses in innate and adaptive immune cells through HVEM-BTLA pathway during ARDS
复制标题
ARDS期间肺驻留间充质干细胞通过HVEM-BTLA途径调节先天性和适应性免疫细胞的炎症反应
DOI：
10.1016/j.yexcr.2020.112155
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发表时间：
2020-10-01
影响因子：
3.7
通讯作者：
Song, Yuanlin
中科院分区：
文献类型：
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作者：
Cheng, Tingting;Feng, Yun;Song, Yuanlin
急性呼吸窘迫综合征（ARDS）是一种由免疫系统过度激活引起的器官衰竭综合征。间充质干细胞（MSC）因其出色的免疫调节能力而被发现在 ARDS 治疗中有效；然而，人们担心输注外源细胞的安全性。我们发现大鼠肺驻留间充质干细胞（LRMSC）（Sca-1（+）CD45（-）CD31（-））在ARDS发病过程中在调节肺部炎症中发挥重要作用。 LRMSCs 可以在体内或体外 LPS 刺激后调节先天性和适应性免疫细胞产生细胞因子（TNF-α、MCP-1 和 IL-10）。我们还发现LRMSCs中疱疹病毒进入介质（HVEM）的表达增强了LRMSCs的免疫调节能力，并且需要在先天性和适应性免疫细胞中表达HVEM配体B和T淋巴细胞衰减因子（BTLA）。这种免疫调节机制的阐明可能为未来动员内源性MSC介导的ARDS治疗提供证据。
Acute respiratory distress syndrome (ARDS) is an organ failure syndrome caused by overactivation of the immune system. Mesenchymal stem cells (MSCs) have been found to be effective in ARDS therapy due to their excellent immunomodulatory abilities; however, people are concerned about the safety of infusing exogenous cells. We found that rat lung-resident mesenchymal stem cells (LRMSCs) (Sca-1(+)CD45(-)CD31(-)) played important roles in regulating inflammation in the lungs during the pathogenesis of ARDS. LRMSCs could regulate the production of cytokines (TNF-alpha, MCP-1, and IL-10) by both innate and adaptive immune cells following LPS stimulation in vivo or in vitro. We also found that Herpes Virus Entry Mediator (HVEM) expression in LRMSCs enhanced the immunomodulatory ability of LRMSCs, and expression of the HVEM ligand B and T Lymphocyte Attenuator (BTLA) in innate and adaptive immune cells was required. The clarification of this immunoregulatory mechanism may provide evidence for ARDS therapy mediated by mobilizing endogenous MSCs in the future.