Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Pulmonary and Clinical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Respiration, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Exp Cell Res. 2020 Oct 1;395(1):112155. doi: 10.1016/j.yexcr.2020.112155. Epub 2020 Jun 27.
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-1CD45CD31) played important roles in regulating inflammation in the lungs during the pathogenesis of ARDS. LRMSCs could regulate the production of cytokines (TNF-α, 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.
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（MSCs）因其出色的免疫调节能力，已被证明在 ARDS 治疗中有效；然而，人们对输注外源性细胞的安全性表示担忧。我们发现，大鼠肺驻留间充质干细胞（LRMSCs）（Sca-1CD45CD31）在 ARDS 发病机制中对调节肺部炎症发挥重要作用。LRMSCs 可以调节先天和适应性免疫细胞在 LPS 刺激体内或体外后产生的细胞因子（TNF-α、MCP-1 和 IL-10）。我们还发现，LRMSCs 中的疱疹病毒进入介质（HVEM）表达增强了 LRMSCs 的免疫调节能力，先天和适应性免疫细胞中 HVEM 配体 B 和 T 淋巴细胞衰减器（BTLA）的表达是必需的。这一免疫调节机制的阐明可能为未来通过动员内源性 MSCs 进行 ARDS 治疗提供证据。
