Monocytic Myeloid-Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells Through IL-15 Secretion.
Monocytic Myeloid-Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells Through IL-15 Secretion.
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DOI：
10.3389/fcell.2022.817402
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发表时间：
2022
影响因子：
5.5
通讯作者：
Rong R
中科院分区：
文献类型：
--
作者：
Cheuk YC;Xu S;Zhu D;Luo Y;Chen T;Chen J;Li J;Shi Y;Zhang Y;Rong R
背景：越来越多的证据表明，间充质干细胞是肌成纤维细胞的前体细胞，在肾脏纤维化中发挥重要作用。MSCs与其他免疫细胞之间的密切相互作用调节着多种纤维化相关疾病的发展。然而，髓系来源的抑制细胞(MDSCs)对MSCs的作用尚不清楚。在此，我们研究了MDSCs对MSCs肌成纤维细胞分化的影响。方法：用转化生长因子-β1(TGFR-β-1)诱导间充质干细胞向肌成纤维细胞分化。用流式细胞仪对M-MDSCs和G-MDSCs进行分选。培养的骨髓间充质干细胞(BM-MSCs)经转化生长因子-β-1诱导分化为肌成纤维细胞。免疫组织化学染色检测肌成纤维细胞分化程度。定量聚合酶链式反应和免疫印迹分析检测肝纤维化相关基因的表达。采用小鼠单侧肾缺血再灌注损伤(IRI)模型，观察M-MDSC上清液或M-MDSC上清液联合IL-15单抗对小鼠肾间充质干细胞(RRMSCs)肌成纤维细胞分化的影响。结果：MDSC培养上清液对MSCs的肌成纤维细胞分化有抑制作用，尤其是M-MDSC培养上清液对MSCs的肌成纤维细胞分化有抑制作用。M-MDSC上清液对MSCs肌成纤维细胞分化的抑制作用部分通过IL-15-Ras-ERK1/2-Smad2/3信号转导途径实现。M-MDSC上清液通过IL-15改善RRMSCs的肾纤维化和肌成纤维细胞分化。此外，在小鼠IRI模型中，M-MDSC上清液增加了M-MDSC在肾脏中的渗透。M-MDSC上清液通过IL-15下调MSCs细胞膜上的黏附和迁移标记CD44。结论：骨髓间充质干细胞培养上清通过IL-15抑制转化生长因子-β1诱导的骨髓间充质干细胞向肌成纤维细胞分化。我们的发现揭示了MDSCs对MSCs肌成纤维细胞分化和黏附的影响，这可能为开发肾纤维化的治疗策略提供新的视角。
Background: Accumulating evidence indicates that mesenchymal stem cells (MSCs) are precursors of myofibroblasts, which play a vital role in renal fibrosis. The close interaction between MSCs and other immune cells regulates the development of multiple fibrosis-related diseases. However, the effect of myeloid-derived suppressor cells (MDSCs) on MSCs remains unexplored. Here, we investigated the effect of MDSCs on the myofibroblastic differentiation of MSCs. Methods: MSCs were induced to undergo myofibroblastic differentiation with transforming growth factor beta 1 (TGF-β1). M-MDSCs and G-MDSCs were sorted by flow cytometry. Supernatants derived from MDSCs were administered to cultured bone marrow MSCs (BM-MSCs) undergoing TGF-β1-induced myofibroblastic differentiation. Myofibroblastic differentiation was evaluated by immunostaining. The expression of fibrosis-related genes was determined by quantitative PCR and western blot analysis. In vitro, M-MDSC supernatant or M-MDSC supernatant with interleukin (IL)-15 mAbs was administered following unilateral renal ischemia-reperfusion injury (IRI) to observe the myofibroblast differentiation of renal resident MSCs (RRMSCs) in a murine model. Results: Myofibroblastic differentiation of MSCs was hindered when the cells were treated with MDSC-derived supernatants, especially that from M-MDSCs. The inhibitory effect of M-MDSC supernatant on the myofibroblastic differentiation of MSCs was partially mediated by IL-15-Ras-Erk1/2-Smad2/3 signaling. Treatment with M-MDSC supernatant ameliorated renal fibrosis and myofibroblastic differentiation in RRMSCs through IL-15. Additionally, M-MDSC supernatant increased M-MDSC infiltration in the kidney in a mouse IRI model. M-MDSC supernatant downregulated the adhesion and migration marker CD44 on the cell membrane of MSCs via IL-15. Conclusion: M-MDSC-derived supernatant inhibited the TGF-β1-induced myofibroblastic differentiation of MSCs through IL-15. Our findings shed new light on the effect of MDSCs on myofibroblastic differentiation and adhesion of MSCs, which might provide a new perspective in the development of treatment strategies for renal fibrosis.
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影响因子：
7.3
作者：
Fu C;Lu Y;Williams MA;Brantly ML;Ventetuolo CE;Morel LM;Mehrad B;Scott EW;Bryant AJ
通讯作者：
Bryant AJ
影响因子：
64.8
作者：
Kuppe C;Ibrahim MM;Kranz J;Zhang X;Ziegler S;Perales-Patón J;Jansen J;Reimer KC;Smith JR;Dobie R;Wilson-Kanamori JR;Halder M;Xu Y;Kabgani N;Kaesler N;Klaus M;Gernhold L;Puelles VG;Huber TB;Boor P;Menzel S;Hoogenboezem RM;Bindels EMJ;Steffens J;Floege J;Schneider RK;Saez-Rodriguez J;Henderson NC;Kramann R
通讯作者：
Kramann R
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1016/j.jaci.2018.08.023
发表时间：
2019-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Ke X;Do DC;Li C;Zhao Y;Kollarik M;Fu Q;Wan M;Gao P
通讯作者：
Gao P
影响因子：
3.7
作者：
Höchst B;Mikulec J;Baccega T;Metzger C;Welz M;Peusquens J;Tacke F;Knolle P;Kurts C;Diehl L;Ludwig-Portugall I
通讯作者：
Ludwig-Portugall I