Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Reprod Immunol. 2023 Mar;156:103818. doi: 10.1016/j.jri.2023.103818. Epub 2023 Jan 31.
There has been limited study on the impact of PBMC therapy in RSA patients with immunological disorders such as Th17 and Treg cell dysregulation, as well as their associated factors. This study aimed to assess the efficacy of PBMC therapy in modulating immune cell frequency, cytokine production, transcription factors, and miRNAs implicated in the regulation of their function, as well as their potential superiority to routine treatments.
Fifty RSA women who had received PBMCs and 50 matched-paired control RSA women who had received the routine treatments were recruited and followed for three months. The frequencies of Th17, Treg, NK, and B cells were assessed using flow cytometry. Thereafter, the gene expression level of the transcription factors and related miRNAs of Treg cell and Th17 cell was quantified using RT-PCR. Then ELISA was employed to assess the cytokine production of Th17 and Treg cells. Finally, the live birth rate and miscarriage rate were evaluated as clinical outcomes in this study.
Flow cytometry analysis revealed that PBMC therapy significantly reduces the frequencies of Th17 and NK cells while enhancing the frequency of Treg cells. RT-PCR analysis confirmed that PBMC therapy significantly downregulates RORγt and upregulates FoxP3. Likewise, RT-PCR analysis showed that PBMC therapy reduces the expression of miR-25, miR-155, and miR-326 while increasing the expression of miR-10a. ELISA results demonstrated that PBMC therapy considerably decreases the concentration of inflammatory cytokines IL-1β, IL-17, and TNF-α and enhances the concentration of anti-inflammatory cytokines IL-10 and TGF-β. Following PBMC therapy live birth rate raised while miscarriage rate reduced.
Our findings suggested that, in contrast to routine treatments, PBMC therapy can significantly modulate the maternal immune system by enhancing the Treg/Th17 paradigm and regulating the expression of Treg and Th17 cell-associated cytokines, transcription factors, and miRNAs. This treatment also can increase the live birth rate in RSA patients.
针对免疫失调（如 Th17 和 Treg 细胞失调）的 RSA 患者，已有有限的研究探讨 PBMC 治疗的影响，以及相关因素。本研究旨在评估 PBMC 治疗调节免疫细胞频率、细胞因子产生、转录因子和 miRNA 的功效，及其相对于常规治疗的潜在优势。
招募了 50 名接受 PBMC 治疗的 RSA 女性患者和 50 名接受常规治疗的匹配 RSA 女性患者作为对照，并随访三个月。采用流式细胞术评估 Th17、Treg、NK 和 B 细胞的频率。随后，采用 RT-PCR 定量测定 Treg 和 Th17 细胞的转录因子和相关 miRNA 的基因表达水平。然后采用 ELISA 评估 Th17 和 Treg 细胞的细胞因子产生。最后，将活产率和流产率评估为该研究的临床结局。
流式细胞术分析显示，PBMC 治疗可显著降低 Th17 和 NK 细胞的频率，同时增加 Treg 细胞的频率。RT-PCR 分析证实 PBMC 治疗可显著下调 RORγt 并上调 FoxP3。同样，RT-PCR 分析显示 PBMC 治疗降低了 miR-25、miR-155 和 miR-326 的表达，同时增加了 miR-10a 的表达。ELISA 结果表明，PBMC 治疗可显著降低促炎细胞因子 IL-1β、IL-17 和 TNF-α的浓度，并增加抗炎细胞因子 IL-10 和 TGF-β的浓度。接受 PBMC 治疗后，活产率提高，流产率降低。
与常规治疗相比，PBMC 治疗通过增强 Treg/Th17 范式并调节 Treg 和 Th17 细胞相关细胞因子、转录因子和 miRNA 的表达，可显著调节母体免疫系统。该治疗还可增加 RSA 患者的活产率。
