A molecule linked to chronic inflammation disrupts the brain's ability to create new neurons - uncovering a pathway with therapeutic potential for neurodegenerative diseases and neurological conditions.
The study, published in Nature Communications, offers insight into how long-term inflammation may contribute to cognitive decline in disorders such as Alzheimer's disease, ageing, depression, and the lingering neurological effects of viral infections.
The scientists discovered that adding a molecule, that is involved in the inflammatory response, to stem cells from the hippocampus prevents the development of new neurons. The formation of new neurons in this region, known as hippocampal neurogenesis, is essential for learning, memory and mood regulation. It is one of the few parts of the human brain where new neurons are made in adults. Altered adult hippocampal neurogenesis is associated with ageing, neurodegeneration, and mood disorders such as depression.
The study focused on cytokines, which are chemical signals that are released by the body in response to a threat, such as a viral infection. Cytokines ultimately act as triggers for the rest of the immune response, which helps the body fight the infection. High cytokine levels are also a hallmark of chronic inflammation.
Viral infection has previously been linked to changes in the ability to create new neurons in part of the hippocampus. However, how exactly infection and inflammatory cytokines affect creation of new neurons was previously unknown.
When researchers added one particular cytokine, called TNF‑α, to human hippocampal stem cells, it prevented them from developing into neurons. Instead, they switched into an "immune alert" state, releasing signals that can attract key immune cells, known as T cells, that drive inflammation, while simultaneously reducing the production of young neurons.
First author Dr Tinne A. D. Nissen, who completed the research as part of her PhD at King's College London, said: "What surprised us most was that the stem cells were not simply impaired by inflammation, they actively adopted behaviours that could potentially sustain immune responses in the brain."
Co-corresponding author Professor Sandrine Thuret, Professor of Neuroscience, King's College London, said: "Our findings reveal a new link between chronic inflammation and the brain's reduced ability to generate new neurons.
Inflammatory signals can effectively redirect hippocampal stem cells away from their normal role of producing neurons and toward supporting immune activity instead.
Professor Sandrine Thuret, Professor of Neuroscience, Institute of Psychiatry, Psychology & Neuroscience.
The researchers also identified an unexpected signalling pathway behind this effect involving type I interferons, molecules typically associated with the body's antiviral defence. By blocking interferon signalling with an existing therapeutic antibody, some of the effects of inflammation were reversed - by restoring production of new neurons and preventing the attraction of T cells involved in the immune response.
Our work uncovers a new mechanism that may help explain why ongoing inflammation is so damaging to brain health. Importantly, it also points to possible treatments to protect brain cells.
Professor Linda S. Klavinskis, Professor of Viral Immunology, Faculty of Life Sciences & Medicine.
This research was a collaboration between the Department of Basic and Clinical Neuroscience at the Institute of Psychiatry, Psychology & Neuroscience, the Department of Infectious Diseases and the Peter Gorer Department of Immunobiology, both at the Faculty of Life Sciences & Medicine.
This research was funded by the Wellcome Trust as part of the Neuro-Immune Interactions in Health & Disease Wellcome Trust PhD Programme, the Medical Research Council UK, a Medical Research Council Discovery Award, a PhD Studentship awarded by the Medical Research Council UK, The Galen and Hilary Weston Foundation, the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London.
TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells (DOI: 10.1038/s41467-026-74104-x) was published in Nature Communications.
