Ahmadifard Reza, Jafarzadeh Abdollah, Mahmoodi Merat, Nemati Maryam, Rahmani Mehdi, Khorramdelazad Hossein, Ayoobi Fatemeh
Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Drug Res (Stuttg). 2023 Apr;73(4):213-223. doi: 10.1055/a-1995-6365. Epub 2023 Feb 8.
Mesenchymal stem cells (MSCs) modulate immune responses, and their immunomodulatory potential can be enhanced using inflammatory cytokines. Here, the modulatory effects of IFN-γ-licensed MSCs on expression of T cell-related chemokines and chemokine receptors were evaluated using an experimental autoimmune encephalomyelitis (EAE) model.
EAE was induced in 3 groups of C57bl/6 mice and then treated with PBS, MSCs and IFN-γ-treated MSCs. The EAE manifestations were registered daily and finally, the brain and spinal cords were isolated for histopathological and gene expression studies.
The clinical scores were lowered in MSCs and IFN-γ-licensed MSCs groups, however, mice treated with IFN-γ-licensed MSCs exhibited lower clinical scores than MSCs-treated mice. Leukocyte infiltration into the brain was reduced after treatment with MSCs or IFN-γ-licensed MSCs compared to untreated group (P<0.05 and P<0.01, respectively). In comparison with untreated EAE mice, treatment with MSCs reduced CCL20 expression (P<0.001) and decreased CXCR3 and CCR6 expression (P<0.02 and P<0.04, respectively). In comparison with untreated EAE mice, treatment with IFN-γ-licensed MSCs reduced CXCL10, CCL17 and CCL20 expression (P<0.05, P<0.05, and P<0.001, respectively) as well as decreased CXCR3 and CCR6 expression (P<0.002 and P<0.02, respectively), whilst promoting expression of CCL22 and its receptor CCR4 (P<0.0001 and P<0.02, respectively). In comparison with MSC-treated group, mice treated with IFN-γ-licensed MSCs exhibited lower CXCL10 and CCR6 expression (P<0.002 and P<0.01, respectively), whereas greater expression of CCL22 and CCR4 (P<0.0001 and P<0.01, respectively).
Priming the MSC with IFN-γ can be an efficient approach to enhance the immunomodulatory potential of MSCs.
间充质干细胞（MSCs）可调节免疫反应，且使用炎性细胞因子可增强其免疫调节潜能。在此，利用实验性自身免疫性脑脊髓炎（EAE）模型评估了经γ干扰素预处理的间充质干细胞对T细胞相关趋化因子及趋化因子受体表达的调节作用。
对3组C57bl/6小鼠诱导EAE，随后分别用磷酸盐缓冲液（PBS）、间充质干细胞及经γ干扰素处理的间充质干细胞进行治疗。每日记录EAE表现，最后分离脑和脊髓用于组织病理学及基因表达研究。
间充质干细胞组和经γ干扰素预处理的间充质干细胞组的临床评分均降低，然而，经γ干扰素预处理的间充质干细胞治疗的小鼠临床评分低于间充质干细胞治疗的小鼠。与未治疗组相比，间充质干细胞或经γ干扰素预处理的间充质干细胞治疗后，脑内白细胞浸润减少（分别为P<0.05和P<0.01）。与未治疗的EAE小鼠相比，间充质干细胞治疗降低了CCL20表达（P<0.001），并降低了CXCR3和CCR6表达（分别为P<0.02和P<0.04）。与未治疗的EAE小鼠相比，经γ干扰素预处理的间充质干细胞治疗降低了CXCL10、CCL17和CCL20表达（分别为P<0.05、P<0.05和P<0.001），并降低了CXCR3和CCR6表达（分别为P<0.002和P<0.02），同时促进了CCL22及其受体CCR4的表达（分别为P<0.0001和P<0.02）。与间充质干细胞治疗组相比，经γ干扰素预处理的间充质干细胞治疗的小鼠CXCL10和CCR6表达较低（分别为P<0.002和P<0.01），而CCL22和CCR4表达较高（分别为P<0.0001和P<0.01）。
用γ干扰素预处理间充质干细胞可能是增强间充质干细胞免疫调节潜能的有效方法。
