NL
DE
Researchers have uncovered how stem cells from umbilical cords can help calm an overactive immune system without shutting it down. The study, published in Scientific Reports, reveals that these mesenchymal stem cells (MSCs) can act as “peacekeepers” of immunity — dialing back harmful inflammation while keeping the body’s natural defenses intact.
The immune system is our body’s defense team, protecting us from bacteria, viruses, and other threats. Normally, it switches on when needed and calms down once the danger is gone. But sometimes the immune system becomes overactive. In that case, the body produces too much inflammation, a process meant to fight infections, but which, in excess, can damage healthy tissues. In the short term, this can cause fever, tiredness, joint aches, or swelling. If the inflammation doesn’t settle down, it can turn into a long-lasting problem. Chronic inflammation wears on the body over time and has been linked to conditions such as heart disease, diabetes, or autoimmune disorders.
In our research, we set out to find a therapeutic “peacekeeper”: something that can calm down an overactive immune system without shutting it off completely or harming it. Mesenchymal stem cells (MSCs), which can be obtained from umbilical cords, show this remarkable ability. They are also easy to obtain, since births happen every day. MSCs are well known for their regenerative and immune-balancing properties.
In our study, we discovered how they influence T cell behavior which forms a major part of the immune system. When T cells were cultured with MSCs, we saw that the MSCs could switch off major “alarm pathways” (ERK and NF-κB) that normally drive inflammation. We found that MSCs increased the expression of a gene called TNIP1. This gene is known to act as a natural brake on inflammatory pathways, which suggests a possible mechanism for how MSCs calm down an overactive immune system. At the same time, MSCs boost genes responsible for T cell migration, which is critical because T cells need to move efficiently to sites of inflammation to resolve immune responses. This dual effect means MSCs can reduce harmful overreactions without disabling the immune system.
Together, these findings reveal how MSCs act as gentle moderators of immunity: calming excessive responses while keeping defenses intact. Understanding these molecular mechanisms opens up new possibilities for therapies to treat chronic inflammation, autoimmune diseases, and even complications after transplantation.
This study was part of the EU Horizon 2020 PREMSTEM grant, aimed at developing a new regenerative stem cell therapy to repair the brain damage caused by premature birth. The study was performed by researcher Ezgi Sengun under the supervision of Renate van der Molen and Marien de Jonge from the Medical Immunology lab at Radboudumc, in collaboration with Daan Ophelders and Tim Wolfs from Maastricht UMC+, and published in Scientific Reports on 30 August 2025.
About the publication
Sengun E, Fröberg J, He X, Eleveld M, Smeets RL, Koenen HJPM, Möller-Hackbarth K, Wolfs TGAM, Ophelders DRMG, Huynen MA, de Jonge MI, van der Molen RG. Mesenchymal stem cells suppress NF-κB and ERK signalling while enhancing chemotaxis in CD4+ T cells. Sci Rep. 2025 Aug 30;15(1):32000. doi: 10.1038/s41598-025-14373-6. PMID: 40885730; PMCID: PMC12398613.
