Human Mesenchymal Stem Cell-Treated Regulatory CD23+ CD43+ B Cells Alleviate Intestinal Inflammation
Human Mesenchymal Stem Cell-Treated Regulatory CD23+ CD43+ B Cells Alleviate Intestinal Inflammation
复制标题
人间充质干细胞处理的调节性 CD23 CD43 B 细胞可减轻肠道炎症
DOI：
10.7150/thno.32260
复制
发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Peng, Yanwen
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyong;Cai, Chuang;Peng, Yanwen
基本原理：间充质干细胞（MSC）已被证明可以通过对多种免疫细胞，特别是调节性B细胞（布雷格细胞）的作用来改善炎症性肠道疾病。然而，人间充质干细胞（hMSCs）处理的布雷格细胞亚群的表型和功能尚不清楚。研究方法：将纯化后的B细胞与MSCs共培养，通过流式细胞仪和体外增殖实验分析B细胞的表型和免疫调节功能。此外，采用三硝基苯磺酸诱导的小鼠结肠炎模型来检测MSC处理的布雷格细胞在体内的功能。结果如下：我们证明，与hMSCs共培养通过上调IL-10表达显著增强了B细胞的免疫调节活性。然后，我们确定了一种新的调节性B细胞群体的特点是CD 23和CD 43表型标记可以诱导hMSCs。CD 23 + CD 43+布雷格细胞通过IL-10依赖性途径显著抑制炎性细胞因子分泌和T细胞增殖。更重要的是，腹膜内注射hMSC改善了小鼠实验性结肠炎模型的临床和组织病理学严重程度，伴随着CD 23 + CD 43+布雷格细胞数量的增加。与CD 23-CD 43- B细胞相比，CD 23 + CD 43 + B细胞过继转移可有效减轻小鼠结肠炎。用CD 23 + CD 43 + B细胞而不是hMSC治疗，显著改善了B细胞耗竭小鼠的结肠炎症状。结论：新的CD 23 + CD 43+布雷格细胞亚群似乎参与hMSC的免疫调节功能，并为阐明hMSC治疗炎症相关疾病的治疗机制提供了新的线索。
Rationale: Mesenchymal stem cells (MSCs) have been demonstrated to ameliorate inflammatory bowel disease by their actions on multiple immune cells, especially on regulatory B cells (Breg cells). However, the phenotypes and functions of human MSCs (hMSCs)-treated Breg cell subsets are not yet clear. Methods: Purified B cells were cocultured with MSCs and the phenotypes and immunomodulatory functions of the B cells were analyzed by FACS and proliferation assays in vitro. Also, a trinitrobenzenesulfonic acid-induced mouse colitis model was employed to detect the function of MSC-treated Breg cells in vivo. Results: We demonstrated that coculturing with hMSCs significantly enhanced the immunomodulatory activity of B cells by up-regulating IL-10 expression. We then identified that a novel regulatory B cell population characterized by CD23 and CD43 phenotypic markers could be induced by hMSCs. The CD23+CD43+ Breg cells substantially inhibited the inflammatory cytokine secretion and proliferation of T cells through an IL-10-dependent pathway. More significantly, intraperitoneal injection of hMSCs ameliorated the clinical and histopathological severity in the mouse experimental colitis model, accompanied by an increase in the number of CD23+CD43+ Breg cells. The adoptive transfer of CD23+CD43+ B cells effectively alleviated murine colitis, as compared with the CD23-CD43- B cells. Treatment with CD23+CD43+ B cells, and not hMSCs, substantially improved the symptoms of colitis in B cell-depleted mice. Conclusion: the novel CD23+CD43+ Breg cell subset appears to be involved in the immunomodulatory function of hMSCs and sheds new light on elucidating the therapeutic mechanism of hMSCs for the treatment of inflammation-related diseases.