Sun Guojing, Wang Yicun, Ti Yunfan, Wang Jun, Zhao Jianning, Qian Hongbo
Department of Orthopedics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
Clin Exp Pharmacol Physiol. 2017 Apr;44(4):455-462. doi: 10.1111/1440-1681.12719.
Bone fractures may result in delayed union (DU) or non-union (NU) in some patients. Evidence suggests that the skewing of the immune system toward the proinflammatory type is a contributing factor. Because B cells were previously found to infiltrate the fracture healing site at abundant levels, we examined the regulatory B cells (Bregs) in DU/NU patients. In bone fracture patients with normal healing, the frequency of interleukin (IL)-10-expressing B cells was significantly upregulated in the early healing process (6 weeks post-surgery) and was downregulated later on (18 weeks post-surgery), whereas in DU/NU patients, the early upregulation of IL-10-expressing B cells was missing. The majority of IL-10-expressing B cells were concentrated in the IgM CD27 fraction in both controls and patients. IgM CD27 B cells effectively suppressed interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-2 expression from CD4 T cells, as well as IFN-γ and TNF-α expression from CD8 T cells. The IgM CD27 B cell-mediated suppression was restricted to the sample from the early healing time point in controls, as the IgM CD27 B cells from normal healing patients later on or from DU/NU patients did not present significant regulatory function. In addition, culturing of CD4 CD25 Tregs with IgM CD27 B cells from controls at early healing time point resulted in higher Foxp3 expression, a function absent in controls at later time point, or in DU/NU patients. In conclusion, our results support a role of B cell-mediated regulation early during the bone healing process.
在一些患者中，骨折可能导致延迟愈合（DU）或不愈合（NU）。有证据表明，免疫系统向促炎型的倾斜是一个促成因素。由于先前发现B细胞大量浸润骨折愈合部位，我们检查了DU/NU患者中的调节性B细胞（Bregs）。在骨折愈合正常的患者中，表达白细胞介素（IL）-10的B细胞频率在愈合早期（术后6周）显著上调，随后在后期（术后18周）下调，而在DU/NU患者中，表达IL-10的B细胞早期上调缺失。在对照组和患者中，大多数表达IL-10的B细胞集中在IgM CD27部分。IgM CD27 B细胞有效抑制CD4 T细胞产生的干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）和IL-2，以及CD8 T细胞产生的IFN-γ和TNF-α。IgM CD27 B细胞介导的抑制作用仅限于对照组早期愈合时间点的样本，因为正常愈合患者后期或DU/NU患者的IgM CD27 B细胞没有显著的调节功能。此外，在早期愈合时间点将CD4 CD25调节性T细胞与对照组的IgM CD27 B细胞一起培养，会导致更高的Foxp3表达，而这在对照组后期或DU/NU患者中不存在此功能。总之，我们的结果支持B细胞介导的调节在骨愈合过程早期发挥作用。
