Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France; Univ Rennes, CHU Rennes, F-35000 Rennes, France.
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France.
Cytokine. 2019 May;117:50-58. doi: 10.1016/j.cyto.2019.02.002. Epub 2019 Feb 28.
BACKGROUND & AIMS: We have reported a significant association between HLA-G expression or the number of hepatic mast cells and liver fibrosis. Here, we investigated the role of HLA-G and mast cells in liver fibrosis, focusing, in particular, on interactions between human mast and stellate cells.
Human mast cells (HMC cell line, CD34-derived mast cells, or tissue-derived mast cells) were co-cultured with purified human hepatic stellate cells (HSCs), and collagen I production by HSCs was evaluated. Mast cells and HSCs were characterized by immunocytochemistry. Various conditions were tested: different times in direct or indirect contact, presence or absence of cytokines, addition or not of HLA-G, and presence or absence of specific protease inhibitors.
The reciprocal interaction between HSCs and mast cells led to the attraction of mast cells to HSCs in vivo and in vitro, and to a significant decrease in collagen production, at all times of co-culture, following the direct or indirect contact of mast cells with HSCs alone or in the presence of TGF-β, IFN-α or IL-10. We identified the diffusible factors involved in collagen I degradation as mast cell proteases. Moreover, HLA-G expression increased during the co-culture of HSCs and mast cells, with HLA-G acting on both mast cells and HSCs, to enhance collagen I degradation.
Mast cells play a beneficial, anti-fibrotic role in liver fibrosis, via the HLA-G-mediated decrease of collagen I. These findings are consistent with high levels of cross-communication between mast cells and hepatic stellate cells and the role of HLA-G.
我们曾报道过 HLA-G 表达或肝肥大细胞数量与肝纤维化之间存在显著关联。在此，我们重点研究了 HLA-G 和肥大细胞在肝纤维化中的作用，尤其是研究了人类肥大细胞和星状细胞之间的相互作用。
将人肥大细胞（HMC 细胞系、CD34 衍生的肥大细胞或组织衍生的肥大细胞）与纯化的人肝星状细胞（HSCs）共培养，并评估 HSCs 产生胶原 I 的情况。通过免疫细胞化学对肥大细胞和 HSCs 进行了特征分析。测试了各种条件：直接或间接接触不同时间、存在或不存在细胞因子、添加或不添加 HLA-G 以及存在或不存在特定的蛋白酶抑制剂。
HSCs 和肥大细胞之间的相互作用导致肥大细胞在体内和体外向 HSCs 迁移，并且在单独接触或在 TGF-β、IFN-α 或 IL-10 存在的情况下，HSCs 与肥大细胞直接或间接接触后，所有共培养时间的胶原产生均显著减少。我们鉴定了参与胶原 I 降解的可扩散因子为肥大细胞蛋白酶。此外，在 HSCs 和肥大细胞共培养期间 HLA-G 表达增加，HLA-G 作用于肥大细胞和 HSCs，以增强胶原 I 降解。
肥大细胞在肝纤维化中发挥有益的抗纤维化作用，通过 HLA-G 介导的胶原 I 减少来实现。这些发现与肥大细胞和肝星状细胞之间的高度交叉通讯以及 HLA-G 的作用一致。
