HVEM Promotes the Osteogenesis of allo-MSCs by Inhibiting the Secretion of IL-17 and IFN-g in Vg4T Cells
HVEM Promotes the Osteogenesis of allo-MSCs by Inhibiting the Secretion of IL-17 and IFN-g in Vg4T Cells
复制标题
HVEM通过抑制Vg4T细胞中IL-17和IFN-g的分泌促进同种异体间充质干细胞的成骨
作者：
何磊;肖军;宋磊;周锐;荣志刚;贺伟峰;代飞
骨缺损是常见的骨科问题，越来越多的组织工程骨 (TEB) 用于修复骨缺损。同种异体间充质干细胞（allo-MSCs）在许多方法中被用作种子细胞来开发TEB构建体，但同种异体移植引起的免疫反应可能导致移植失败。 Vγ4T（Vg4T）细胞在移植后早期介导免疫反应中发挥重要作用；因此，我们想验证通过疱疹病毒进入介质（HVEM）/B和T淋巴细胞衰减因子（BTLA）信号抑制Vg4T细胞是否可以促进移植区域的MSCs成骨。体外实验表明，共培养后MSCs和Vg4T细胞的成骨分化能力减弱，培养上清液中白细胞介素17（IL-17）和干扰素-g（IFN-g）水平升高。 HVEM转染的MSCs（MSCs-HVEM）与Vg4T细胞共培养后仍表现出成骨分化活性，并且共培养上清液中IL-17和IFN-g的水平显着降低。体内实验表明，去除Vg4T细胞后，移植区域的炎症减少，成骨修复增强。 MSCs-HVEM 还可以始终有助于减少移植区域的炎症并增强野生型 (WT) 小鼠的骨修复。因此，我们的实验证实HVEM可以通过抑制Vg4T细胞分泌IL-17和IFN-g来促进allo-MSCs的成骨。
Bone defects are a common orthopaedic concern, and an increasing number of tissueengineered bones (TEBs) are used to repair bone defects. Allogeneic mesenchymal stem.cells (allo-MSCs) are used as seed cells in many approaches to develop TEB constructs,.but the immune response caused by allogeneic transplantation may lead to transplant.failure. V gamma 4 T (Vg4T) cells play an important role in mediating the immune response.in the early stage after transplantation; therefore, we wanted to verify whether suppressing.Vg4T cells by herpesvirus entry mediator (HVEM)/B and T lymphocyte attenuator (BTLA).signalling can promote MSCs osteogenesis in the transplanted area. In vitro experiments.showed that the osteogenic differentiation of MSCs and Vg4T cells was weakened after.co-culture, and an increase in interleukin-17 (IL-17) and interferon-g (IFN-g) levels was.detected in the culture supernatant. HVEM-transfected MSCs (MSCs-HVEM) still.exhibited osteogenic differentiation activity after co-culture with Vg4T cells, and the.levels of IL-17 and IFN-g in the co-culture supernatant were significantly reduced. In.vivo experiments revealed that inflammation in the transplanted area was reduced and.osteogenic repair was enhanced after Vg4T cells were removed. MSCs-HVEM can also.consistently contribute to reduced inflammation in the transplanted area and enhanced.bone repair in wild-type (WT) mice. Therefore, our experiments verified that HVEM can.promote the osteogenesis of allo-MSCs by inhibiting IL-17 and IFN-g secretion from.Vg4T cells.