Liu Ting, Ren Jun, Wang Wei, Wei Xia-wei, Shen Guo-bo, Liu Yan-tong, Luo Min, Xu Guang-chao, Shao Bin, Deng Sen-yi, He Zhi-yao, Liang Xiao, Liu Yu, Wen Yan-Zhu, Xiang Rong, Yang Li, Deng Hong-xin, Wei Yu-quan
State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
Department of Immunology, Medical School of Nankai University, 94 Weijin Road, Tianjin 300071, PR China.
Sci Rep. 2015 Nov 13;5:16760. doi: 10.1038/srep16760.
The adoptive transfer of the natural regulatory B cells and macrophages should be a useful treatment for inflammation and autoimmune disease. However, it is usually difficult to isolate these cells from the tissues and expand them. Here, we investigated the feasibility of adoptively transferring peritoneal cells (PCs) as a treatment for DSS-induced colitis. We found that peritoneal cavity can provide an easily accessible site for harvesting enough number of PCs, namely, two-dose PCs for the treatment from a mouse in one operation. Adoptive therapy of these cells from healthy mice or those with disease is effectively in reducing the disease activity score. The natural B cells and macrophages of the infused PCs can selectively migrate to lesion sites and regulate the expression of Stat3, NF-κB, Smad3 and Smad7. Additionally, PCs exert dual activity of IL-10 and TGF-β secreted spontaneously by both peritoneal B cells and macrophages, which in turn enhance the induction of regulatory B cells and Macrophages in microenvironment of inflammation. Moreover, PCs can re-establish immunological tolerance in the OVA-immunized mice. Thus, our findings provide a new strategy for colitis therapy and could be of importance in additional exploration of other inflammation and autoimmune diseases therapy.
天然调节性B细胞和巨噬细胞的过继性转移应是治疗炎症和自身免疫性疾病的一种有效方法。然而，通常很难从组织中分离出这些细胞并进行扩增。在此，我们研究了过继性转移腹腔细胞（PCs）治疗葡聚糖硫酸钠（DSS）诱导的结肠炎的可行性。我们发现腹腔可以提供一个易于获取的部位，以收获足够数量的PCs，即在一次操作中从一只小鼠获取用于治疗的两剂量PCs。对来自健康小鼠或患病小鼠的这些细胞进行过继性治疗可有效降低疾病活动评分。输注的PCs中的天然B细胞和巨噬细胞可选择性迁移至病变部位，并调节信号转导和转录激活因子3（Stat3）、核因子κB（NF-κB）、Smad3和Smad7的表达。此外，PCs发挥由腹腔B细胞和巨噬细胞自发分泌的白细胞介素10（IL-10）和转化生长因子β（TGF-β）的双重活性，这反过来又增强了炎症微环境中调节性B细胞和巨噬细胞的诱导。此外，PCs可在卵清蛋白免疫的小鼠中重新建立免疫耐受。因此，我们的研究结果为结肠炎治疗提供了一种新策略，并且在进一步探索其他炎症和自身免疫性疾病的治疗方面可能具有重要意义。
