Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39-CD73 signaling pathway
Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39-CD73 signaling pathway
复制标题
人牙龈源性间充质干细胞通过靶向CD39(-)CD73信号通路治疗狼疮性肾炎
DOI：
10.1016/j.jaut.2020.102491
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发表时间：
2020-09-01
影响因子：
12.8
通讯作者：
Zheng, Song Guo
中科院分区：
文献类型：
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作者：
Dang, Junlong;Xu, Zhenjian;Zheng, Song Guo
细胞特异性和细胞因子靶向治疗在系统性红斑狼疮 (SLE) 中表现不佳。间充质干细胞（MSC）已成为解决自身免疫性疾病失调的一种新疗法，但也有其局限性。人牙龈来源的间充质干细胞 (GMSC) 在调节免疫反应方面具有优越性。在这里，我们证明 GMSC 的过继转移归巢并维持在肾脏中，并且在自发性狼疮肾炎模型中具有强大的治疗效果。具体而言，GMSC 通过直接抑制 B 细胞活化、增殖和分化来限制自身抗体的产生以及蛋白尿，降低浆细胞的频率和狼疮性肾炎组织病理学评分。 CD39-CD73 通路的阻断显着消除了 GMSC 的体外和体内抑制能力，并凸显了该信号通路在 SLE 中的重要性。总的来说，GMSC 的操作为治疗 SLE 和其他自身免疫性疾病患者提供了一种有前景的策略。
Cell specific and cytokine targeted therapeutics have underperformed in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) have emerged as a novel therapy to address the dysregulation in autoimmune diseases but also have limitations. Human gingiva derived MSCs (GMSCs) are superior in regulating immune responses. Here, we demonstrate that the adoptive transfer of GMSCs homes to and maintains in the kidney and has a robust therapeutic effect in a spontaneous lupus nephritis model. Specifically, GMSCs limits the development of autoantibodies as well as proteinuria, decreases the frequency of plasma cells and lupus nephritis histopathological scores by directly suppressing B cells activation, proliferation and differentiation. The blockage of CD39-CD73 pathway dramatically abrogates the suppressive capacities of GMSCs in vitro and in vivo and highlights the significance of this signaling pathway in SLE. Collectively, manipulation of GMSCs provides a promising strategy for the treatment of patients with SLE and other autoimmune diseases.