Sengun Ezgi, Fröberg Janeri, He Xuehui, Eleveld Marc, Smeets Ruben L, Koenen Hans J P M, Möller-Hackbarth Katja, Wolfs Tim G A M, Ophelders Daan R M G, Huynen Martijn A, de Jonge Marien I, van der Molen Renate G
Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Centre Nijmegen, Radboud Institute for Molecular Life Sciences, Route 469, Geert Grooteplein 10, PO-Box 9101, 6500 HB, Nijmegen, The Netherlands.
Global Rare Disease, Chiesi Pharma AB, 17165, Solna, Sweden.
Sci Rep. 2025 Aug 30;15(1):32000. doi: 10.1038/s41598-025-14373-6.
Inflammation is regulated by immune cells, with CD4 T cells playing a key role in its progression and resolution. Modulating their response is crucial for controlling inflammation, and mesenchymal stem cells (MSCs) have emerged as a promising therapeutic target due to their immunomodulatory properties. We previously showed that umbilical cord derived MSCs (UC-MSCs) induce a memory response in TCR-activated CD4 T cells, and here, we investigated the underlying mechanisms through gene expression analysis at different time points. Our results demonstrated that TCR activation is required for UC-MSCs to induce this memory response. Pathway analysis revealed that UC-MSCs induced the expression of genes that negatively regulate immune signalling pathways. This was further supported by phosphoflow cytometry, which showed suppression of the NF-κB and ERK pathways. Additionally, UC-MSCs enhanced the expression of genes related to CD4 T cell adhesion and migration at 12 and 24 h. Notably, TNIP1 emerged as a potential key regulator of UC-MSCs-mediated immune modulation. This study provides new insights into how UC-MSCs influence CD4 T cell responses and highlights molecular targets for further investigation into UC-MSCs-driven immune regulation.
炎症由免疫细胞调节，其中CD4 T细胞在炎症的进展和消退中起关键作用。调节它们的反应对于控制炎症至关重要，而间充质干细胞（MSCs）因其免疫调节特性已成为一个有前景的治疗靶点。我们之前表明，脐带间充质干细胞（UC-MSCs）在TCR激活的CD4 T细胞中诱导记忆反应，在此，我们通过在不同时间点进行基因表达分析来研究其潜在机制。我们的结果表明，UC-MSCs诱导这种记忆反应需要TCR激活。通路分析显示，UC-MSCs诱导了负调节免疫信号通路的基因表达。磷酸化流式细胞术进一步支持了这一点，其显示NF-κB和ERK通路受到抑制。此外，UC-MSCs在12小时和24小时增强了与CD4 T细胞黏附和迁移相关的基因表达。值得注意的是，TNIP1成为UC-MSCs介导的免疫调节的潜在关键调节因子。这项研究为UC-MSCs如何影响CD4 T细胞反应提供了新的见解，并突出了分子靶点，以便进一步研究UC-MSCs驱动的免疫调节。
Cell Mol Biol Lett. 2025-7-10
Comb Chem High Throughput Screen. 2024-5-15
Signal Transduct Target Ther. 2023-6-19
Signal Transduct Target Ther. 2021-12-13
J Immunother Cancer. 2021-9
Zotero 插件