肺纤维化（PF）是由肺损伤及过度炎症反应引起的严重间质性肺病，发病机制不明，缺乏有效的治疗方法，死亡率仍居高不下。研究表明，间充质干细胞（MSCs）在治疗PF中具有免疫调节和组织修复功能，此外，MSCs免疫调节功能可被炎症微环境诱导的自噬所抑制。我们前期发现：人胎盘胎儿来源MSCs（fPMSCs）可改善PF症状，同时，PF体内外炎症微环境诱导了fPMSCs自噬的发生。由此我们推测PF炎症环境诱导的自噬会影响fPMSCs的免疫调节功能及其对PF的疗效。在此基础上，本项目拟完成：1.确定PF炎症微环境与fPMSCs自噬发生的相关性；2.研究自噬对fPMSCs免疫调节功能的调控作用及分子机制；3.明晰干预fPMSCs自噬的发生对PF治疗的影响及机理。本项目的实施将部分明确PF炎症环境诱导的自噬对fPMSCs免疫调节功能的调控机制，为优化MSCs治疗PF的新策略提供了理论基础和实验依据。

Pulmonary fibrosis (PF) is a pulmonary interstitial disease caused by lung injury and inflammatory response. The mechanism caused PF is still unclear. Clinically, there is still a lack of effective treatment to PF, and its mortality rate remains high. Some studies have demonstrated that mesenchymal stem cells (MSCs) play an important immunomodulatory and tissue repair role in the PF treatment. More importantly, the autophagy induced by inflammatory microenvironment plays a critical role in regulating immunomodulatory properties of MSCs. Our recent work discovered that human placental MSCs of fetal origin (fPMSCs) have the ability of reversing the pathological progress of PF. Besides this, we clarified that inflammatory microenvironment associated with PF can induce autophagy of MSCs in vitro and in vivo. Thus we hypothesize that the PF inflammatory microenvironment can trigger autophagy of fPMSCs, then affect their therapeutic potential to PF. Based on these results, the present project is designed to accomplish the following works: 1. to ascertain the regulatory relationship between autophagy of fPMSCs and PF inflammatory microenvironment in vivo and in vitro; 2. to analyze the effects and mechanism of autophagy in regulating immunomodulatory functions of fPMSCs; 3. to clarify whether autophagy influences the therapeutic effects of fPMSCs on PF and its potential principle. The results of these studies will partialy illustrate the functions and mechanism of fPMSCs’ immunomodulatory properties regulated by autophagy in a PF inflammatory microenvironment. This will provide the theoretical basis and experimental evidence for new strategies to optimize MSC treatment for PF.