King’s College London Research, nature communicationsprovides insight into how long-term inflammation contributes to cognitive decline in diseases such as Alzheimer’s disease, aging, depression, and the lingering neurological effects of viral infections.
Scientists have discovered that adding molecules involved in inflammatory responses to stem cells in the hippocampus impedes the development of new neurons. The formation of new neurons in this region, known as hippocampal neurogenesis, is essential for learning, memory, and regulating mood. It is one of the few parts of the human brain where new neurons are created in adulthood. Changes in adult hippocampal neurogenesis are associated with aging, neurodegeneration, and mood disorders such as depression.
The study focused on cytokines, which are chemical signals released by the body in response to threats such as viral infections. Cytokines ultimately act as triggers for the rest of the immune response, helping the body fight infections. High cytokine levels are also a hallmark of chronic inflammation.
Viral infections have previously been associated with changes in the ability of parts of the hippocampus to generate new neurons. However, until now it was unknown how infection and inflammatory cytokines affect the generation of new neurons.
When researchers added a specific cytokine called TNF-α to human hippocampal stem cells, the stem cells were prevented from developing into neurons. Instead, they switched to a state of “immune alarm” and released signals that attracted important immune cells known as T cells, which caused inflammation and reduced the production of new nerve cells.
“What surprised us most was that the stem cells were not just compromised by inflammation, but that they actively adopted behaviors that could potentially sustain an immune response in the brain,” said lead author Dr. Ting A.D. Nissen, who completed the study as part of his PhD at King’s College London.
Our findings reveal a new link between chronic inflammation and a reduced ability of the brain to generate new neurons.
Inflammatory signals can effectively redirect hippocampal stem cells away from their normal role of generating neurons and instead towards supporting immune activity. ”
Professor Sandrine Thuret, co-corresponding author, Professor of Neuroscience, King’s College London
The researchers also identified an unexpected signaling pathway behind this effect that involves type I interferon, a molecule normally associated with the body’s antiviral defenses. Blocking interferon signaling with existing therapeutic antibodies reversed some of the effects of inflammation by restoring the production of new neurons and preventing the recruitment of T cells involved in the immune response.
Co-author Professor Linda S. Kravinskis, Professor of Viral Immunology at King’s College London, added: “Our study reveals a new mechanism that may help explain why ongoing inflammation has such a negative impact on brain health. Importantly, it also points to possible treatments to protect or restore the brain’s ability to regenerate.”
This research is a collaboration between the Department of Infectious Diseases, School of Life Sciences and Medicine, and the Department of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London.
This research was funded by the Wellcome Trust as part of the ‘Neuroimmune Interactions in Health and Disease Wellcome Trust PhD Programme’ and received funding from the UK Medical Research Council, the Medical Research Council Discovery Award, a PhD studentship awarded by the UK Medical Research Council, the Galen and Hilary Weston Foundation, the National Institute for Health Research (NIHR) Biomedical Research Center based at Guy’s and St Thomas NHS Foundation Trust, and King’s College London.
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Reference magazines:
Nissen, TAD, Others. (2026) TNF-α induces type I IFN signaling to suppress neurogenesis and recruit T cells. nature communications. DOI: 10.1038/s41467-026-74104-x. https://www.nature.com/articles/s41467-026-74104-x
