Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland.
Int Immunopharmacol. 2023 Aug;121:110326. doi: 10.1016/j.intimp.2023.110326. Epub 2023 Jun 6.
In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.
为了预防 RPL 患者流产，本研究旨在确定淋巴细胞免疫疗法（LIT）在改变细胞、细胞因子、转录因子和 microRNAs 产生的免疫反应方面的效果如何。本研究纳入了 200 例 RPL 患者和 200 例健康对照者。通过流式细胞术，可以比较淋巴细胞治疗前后细胞的频率。实时 PCR 用于评估转录因子、细胞因子和 microRNAs 的基因表达水平。ELISA 方法用于评估血清中细胞因子分泌水平。健康对照组和 RPL 组之间的免疫谱初步评估显示，RPL 组中 Th17、NK、B 细胞的频率较高，而 Treg 细胞的频率较低。此外，与对照组相比，RPL 组中促炎细胞因子的 mRNA 和蛋白水平表达增加。相反，抗炎细胞因子在 RPL 患者中表达降低。LIT 后 RPL 病例中 Th17 和 Treg 淋巴细胞的频率分别降低和增加。Th17 和 Treg 细胞的转录因子 RORγt 和 FoxP3 mRNA 表达也得到了相同的结果。LIT 后 RPL 患者 NK 细胞的细胞毒性降低。LIT 后 miR-326a 和 miR-155 的表达降低，但 miR-146a 和 miR-10a 的表达在 RPL 病例中增加。LIT 在 RPL 病例中引起抗炎和促炎细胞因子的升高和调节。我们的数据表明，淋巴细胞治疗可以通过调节炎症状态，成为具有免疫背景的 RPL 患者的有效治疗药物。
