Mesenchymal stem cells suppress NF-κB and ERK signalling while enhancing chemotaxis in CD4⁺ T cells

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.