CD14型
依维莫司
免疫系统
获得性免疫系统
树突状细胞
CD11c公司
抗原
单核细胞
免疫学
免疫检查点
生物
先天免疫系统
癌症研究
流式细胞术
PI3K/AKT/mTOR通路
免疫疗法
细胞生物学
信号转导
表型
生物化学
遗传学
基因
作者
Bahram Naseri,Amirhossein Mardi,Arezou Khosrojerdi,Elham Baghbani,Leili Aghebati‐Maleki,Amirhossein Hatami‐Sadr,Javad Ahmadian Heris,Shabnam Eskandarzadeh,Mahshid Kafshdouz,Nazila Alizadeh,Alireza Isazadeh
标识
DOI:10.1016/j.humimm.2024.110798
摘要
Antigen-specific T-cell immunity is provided by dendritic cells (DCs), which are specialized antigen-presenting cells. Furthermore, they establish a link between innate and adaptive immune responses. Currently, DC modification is a new approach for the therapy of several disorders. During solid organ transplantation, Everolimus, which is a mammalian target of rapamycin (mTOR) inhibitor, was initially utilized to suppress the immune system's functionality. Due to the intervention of Everolimus in various signaling pathways in cells and its modulatory properties on the immune system, this study aims to investigate the effect of treatment with Everolimus on the maturation and expression of immune checkpoint genes in monocyte-derived DCs. To isolate monocytes from PBMCs, the CD14 marker was used via the MACS method. Monocytes were cultured and induced to differentiate into monocyte-derived DCs by utilizing GM-CSF and IL-4 cytokines. On the fifth day, immature DCs were treated with Everolimus and incubated for 24 h. On the sixth day, the flow cytometry technique was used to investigate the effect of Everolimus on the phenotypic characteristics of DCs. In the end, the expression of immune checkpoint genes in both the Everolimus-treated and untreated DCs groups was assessed using the real-time PCR method. The findings of this research demonstrated that the administration of Everolimus to DCs led to a notable rise in human leukocyte antigen (HLA)-DR expression and a decrease in CD11c expression. Furthermore, there was a significant increase in the expression of immune checkpoint molecules, namely CTLA-4, VISTA, PD-L1, and BTLA, in DCs treated with Everolimus. The findings of this study show that Everolimus can target DCs and affect their phenotype and function in order to shift them toward a partially tolerogenic state. However, additional research is required to gain a comprehensive understanding of the precise impact of Everolimus on the activation status of DCs.
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