Impaired B Cell Inhibition by Lupus Bone Marrow Mesenchymal Stem Cells Is Caused by Reduced CCL2 Expression

间充质干细胞 系统性红斑狼疮 四氯化碳 B细胞 骨髓 免疫学 狼疮性肾炎 干细胞 体内 医学 癌症研究 炎症 生物 趋化因子 细胞生物学 抗体 内科学 疾病 生物技术
作者
Nan Che,Xia Li,Lu Zhang,Rui Li,Haifeng Chen,Xiang Gao,Songtao Shi,Wanjun Chen,Lingyun Sun
出处
期刊:Journal of Immunology [The American Association of Immunologists]
卷期号:193 (10): 5306-5314 被引量:70
标识
DOI:10.4049/jimmunol.1400036
摘要

Abstract Mesenchymal stem cells (MSC) from healthy human and normal mice can inhibit normal B cell proliferation, differentiation, and Ab secretion in vitro. However, it remains unknown whether MSC from lupus-like mice and patients with systemic lupus erythematosus (SLE) exhibit the same immunoregulatory activity as normal MSC for B cell inhibition and, if not, what the underlying molecular mechanism would be. In this study, we showed that bone marrow–derived MSCs from lupus-like mice and SLE patients had an impairment in suppressing normal B cell proliferation and differentiation, which was caused by the reduction of CCL2 levels. Knockdown of CCL2 in normal MSC damaged their suppressive capacity for B cells. Conversely, overexpression of CCL2 in lupus MSCs restored their immunoregulatory ability for B cells in vitro and ameliorated the pathology of lupus nephritis and serological changes in MRL/lpr mice in vivo. Mechanistically, MSC-mediated B cell inhibition was dependent on matrix metalloproteinase proteolytic processing of CCL2. These findings reveal a novel function of CCL2 in B cell regulation by MSCs and suggest that CCL2 manipulation on MSCs may serve as a potential pathway for developing the more effective MSC-based therapy in autoimmune diseases associated with B cell activation, such as SLE.
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