The anti-fibrotic role of mast cells in the liver is mediated by HLA-G and interaction with hepatic stellate cells
The anti-fibrotic role of mast cells in the liver is mediated by HLA-G and interaction with hepatic stellate cells
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DOI：
10.1016/j.cyto.2019.02.002
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发表时间：
2019-05-01
期刊：
影响因子：
3.8
通讯作者：
Samson, Michel
中科院分区：
文献类型：
--
作者：
Amiot, Laurence;Vu, Nicolas;Samson, Michel
背景与目的：我们已经报道了HLA-G表达或肝肥大细胞数量与肝纤维化之间的显著关联。在这里，我们研究了HLA-G和肥大细胞在肝纤维化中的作用，特别关注人肥大细胞和星状细胞之间的相互作用。方法：将人肥大细胞（HMC细胞系、cd34来源的肥大细胞或组织来源的肥大细胞）与纯化的人肝星状细胞（hsc）共培养，并评估hsc产生的I型胶原。肥大细胞和造血干细胞用免疫细胞化学进行表征。测试了各种条件：直接或间接接触的不同时间，细胞因子的存在或不存在，HLA-G的添加或不添加，以及特定蛋白酶抑制剂的存在或不存在。结果：在体内和体外，造血干细胞和肥大细胞之间的相互作用导致肥大细胞被造血干细胞吸引，并且在共培养的所有时间，肥大细胞与造血干细胞单独或在tgf - β、ifn - α或IL-10存在下直接或间接接触后，胶原生成显著减少。我们确定了参与I型胶原降解的扩散因子为肥大细胞蛋白酶。此外，在造血干细胞和肥大细胞共培养过程中，HLA-G表达增加，HLA-G同时作用于肥大细胞和造血干细胞，促进I型胶原降解。结论：肥大细胞通过HLA-G介导的胶原蛋白i的减少，在肝纤维化中发挥有益的抗纤维化作用。这些发现与肥大细胞和肝星状细胞之间的高水平交叉通讯以及HLA-G的作用是一致的。
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.Methods: 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.Results: 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-beta, IFN-alpha 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.Conclusions: 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.