Elucidation of the molecular mechanisms of CD4 T cell-induced osteoblastic hematopoietic niche impairments after bone marrow transplantation

使用小鼠allo-HSCT模型，我们发现成纤维细胞/间充质干细胞和成骨细胞在allo-HSCT后早期受损，并且成骨细胞从X射线辐射介导的损伤中的恢复在GVHD小鼠中受损。成骨细胞损伤部分依赖于宿主非造血细胞上的MHC II类，而成骨细胞系的杀伤和生长抑制需要异源CD 4 T细胞的活化。基于基因表达分析，我们确定了成骨细胞抑制因子，这是特异性表达的异源CD 4 T细胞，作为一个候选调解人的成骨细胞损害BM GVHD。我们预计我们的结果将有助于早期诊断标志物以及针对BM GVHD的预防和治疗策略的开发。

Using mouse allo-HSCT models, we revealed that fibroblasts/mesenchymal stem cells as well as osteoblasts were damaged early after allo-HSCT, and that the recovery of osteoblasts from X-ray irradiation-mediated damage was impaired in mice with GVHD. The osteoblast impairments were partially dependent on MHC class II on host non-hematopoietic cells, whereas the killing and growth inhibition of osteoblast cell lines required activation of allo-CD4 T cells. Based on gene expression analyses, we identified an osteoblast inhibitory factor, which was specifically expressed in allo-CD4 T cells, as a candidate mediator of osteoblast impairment during BM GVHD. We expect that our results would contribute to the development of early diagnostic markers as well as the preventive and therapeutic strategies against BM GVHD.