干扰素γ处理的间充质干细胞在实验性自身免疫性脑脊髓炎动物模型中调节T细胞相关趋化因子和趋化因子受体

IF 1.7 Q3 PHARMACOLOGY & PHARMACY Drug Research Pub Date : 2023-04-01 DOI:10.1055/a-1995-6365
Reza Ahmadifard, Abdollah Jafarzadeh, Merat Mahmoodi, Maryam Nemati, Mehdi Rahmani, Hossein Khorramdelazad, Fatemeh Ayoobi
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引用次数: 0

摘要

背景:间充质干细胞(MSCs)调节免疫反应,其免疫调节潜能可通过炎症细胞因子增强。在这里,使用实验性自身免疫性脑脊髓炎(EAE)模型评估IFN-γ许可的MSCs对T细胞相关趋化因子和趋化因子受体表达的调节作用。材料与方法:分别用PBS、MSCs和IFN-γ处理的MSCs诱导3组C57bl/6小鼠EAE。每天记录EAE表现,最后分离脑组织和脊髓进行组织病理学和基因表达研究。结果:MSCs组和IFN-γ授权MSCs组的临床评分均降低,但IFN-γ授权MSCs组小鼠的临床评分低于MSCs组小鼠。与未治疗组相比,经MSCs或经IFN-γ许可的MSCs治疗后,白细胞对脑的浸润减少(结论:用IFN-γ刺激MSC可能是增强MSCs免疫调节潜能的有效方法。
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Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis.

Background: 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.

Material and methods: 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.

Results: 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).

Conclusion: Priming the MSC with IFN-γ can be an efficient approach to enhance the immunomodulatory potential of MSCs.

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来源期刊
Drug Research
Drug Research PHARMACOLOGY & PHARMACY-
CiteScore
3.50
自引率
0.00%
发文量
67
期刊介绍: Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.
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