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首页> 外文期刊>The FASEB Journal >Regulation and function of immunosuppressive molecule human leukocyte antigen G5 in human bone tissue
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Regulation and function of immunosuppressive molecule human leukocyte antigen G5 in human bone tissue

机译：免疫抑制分子人白细胞抗原G5在人骨组织中的调节和功能

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Bone-marrow mesenchymal stem cells (MSCs) are the origin of bone-forming cells with immunomodulation potential. HLA-G5 is among the generated immunosuppressive molecules. HLA-G proteins play a crucial role in promoting the acceptance of allografts. However, the mechanisms regulating the expression of HLA-G5 in human MSCs are unknown. We induced differentiation of MSCs and found that HLA-G5 was greatly up-regulated only in osteoblastic cells (+63% for mRNA). Growth plates and bone callus postfracture in adults showed that only bone-lining cells and mesenchymal progenitors were positive for HLA-G5. Use of gene silencing and dominant-negative factors revealed that HLA-G5 depends on the expression and function of the skeletogenesis master genes RUNX2 and DLX5. In addition, HLA-G5 could directly inhibit osteoclastogenesis by acting on monocytes through SHP1. However, in mature osteoblasts, the expression of HLA-G5 protein was greatly suppressed whereas the proosteoclastogenic factor, RANKL, was concomitantly increased. Down-regulation of HLA-G5 expression during the maturation of osteoblasts was due to binding of the repressor GLI3, a signal transducer of the Hedgehog pathway, to the GLI binding element within the HLA-G promoter. Our findings show that mesenchymal progenitors and osteoblastic cells specifically express HLA-G5 during osteogenesis, with a key role in bone homeostasis.—Deschaseaux, F., Gaillard, J., Langonné, A., Chauveau, C., Naji, A., Bouacida, A., Rosset, P., Heymann, D., De Pinieux, G., Rouas-Freiss, N., Sensébé, L. Regulation and function of immunosuppressive molecule human leukocyte antigen G5 in human bone tissue.
机译：骨髓间充质干细胞（MSCs）是具有免疫调节电位的骨形成细胞的起源。 HLA-G5是生成的免疫抑制分子中。 HLA-G蛋白在促进同种异体移植物的接受方面发挥着至关重要的作用。然而，调节人体MSCs中HLA-G5表达的机制是未知的。我们诱导MSCs的分化，发现HLA-G5仅在骨细胞（mRNA的63％）中大大上调。成年人的生长板和骨愈伤组织出现后，只有骨衬里细胞和间充质祖细胞对HLA-G5呈阳性。使用基因沉默和主导负因子显示HLA-G5取决于骨膜发育母基因Runx2和DLX5的表达和功能。此外，HLA-G5可以通过在通过SHP1上作用于单核细胞来直接抑制骨核细胞发生。然而，在成熟的成骨细胞中，HLA-G5蛋白的表达大得多抑制，而前偶联因子RANKL伴随着。在成骨细胞成熟期间HLA-G5表达的下调是由于抑制剂GLI3的结合，刺痛的途径的信号传感器，在HLA-G启动子内的GLI结合元素中。我们的研究结果表明，间充质祖细胞和成骨细胞在骨质发生期间特异性表达HLA-G5，在骨稳态中具有关键作用。-deschaseaux，F.，Gaillard，J.，Langonné，A.，Chauveau，C.，Naji，A. ，Bouacida，A.，Rosset，P.，Heymann，D.，De Pinieux，G.，Rouas-Freiss，N.，Sensébé，L.在人骨组织中免疫抑制分子人白细胞抗原G5的调节和功能。

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