Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury

作者：Zhonghua Lu, Wei Chang, Shanshan Meng, Xiuping Xu, Jianfeng Xie, Fengmei Guo, Yi Yang, Haibo Qiu, Ling Liu · 发表于：Stem Cell Research & Therapy · 年份：2019 · DOI：10.1186/s13287-019-1488-2 · 被引用次数：150 · 研究领域：Mesenchymal stem cell research、Immune cells in cancer、Immunotherapy and Immune Responses

BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF) and to induce the differentiation of dendritic cells (DCs) into tolerogenic dendritic cells (DCregs) and participate in the immune response. However, whether MSCs induce the production of DCregs by secreting HGF to alleviate early ALI remains unclear. We observed that the protective effect of mouse bone marrow-derived MSCs against lipopolysaccharide (LPS)-induced ALI was achieved by inducing mature DCs (mDCs) to differentiate into DCregs, and its mechanism is related to the activation of the HGF/Akt pathway. METHODS: MSCs or MSCs with overexpression or knockdown of HGF were cocultured with DCs derived from mouse bone marrow using a Transwell system for 3 days. Moreover, we used MSCs or MSCs with overexpression or knockdown of HGF to treat LPS-induced ALI mice for 24 h. Flow cytometry was performed to measure the phagocytosis, accumulation, and maturation of DCs, as well as proliferation of T cells. Lung injury was estimated by lung wet weight to body weight ratio (LWW/BW) and histopathological analysis. Furthermore, we used the Akt inhibitor MK-2206 in a coculture system to elucidate the role of the HGF/Akt pathway in regulating the differentiation of DCs into regulatory DCs and relieving lung injury in early ALI mice. RESULTS: Immature DCs (imDCs) were induced to mature after 24 h of LPS (50 ng/ml) stimulation. MSCs or HGF induced the di...