Summary: A new study demonstrated that introducing inflammatory signaling molecules directly into human hippocampal stem cells brings new neuron production to a dead stop. Instead of simply dying or becoming damaged, the brain’s neural stem cells actively abandon their regenerative responsibilities, transforming into an “immune alert” state that actively fuels localized neuroinflammation.
Key Facts
- The Cytokine Intrusion: The team analyzed the behavior of cytokines, specialized chemical signaling proteins released by the body during immune threats, such as severe viral infections. While transient cytokine spikes help clear out acute sickness, sustained high levels are a classic hallmark of devastating chronic inflammation.
- The TNF-α Standstill: When researchers exposed human hippocampal stem cells to a specific pro-inflammatory cytokine called Tumor Necrosis Factor alpha (TNF-α), the cellular birth pipeline froze. The stem cells completely ceased differentiating into mature, functional neurons.
- The “Immune Alert” Takeover: To the shock of the investigators, the stem cells weren’t merely passive casualties of chemical stress. Instead, they actively assumed a hostile, immune-supportive behavior, pumping out high-alert chemical signals designed to recruit inflammatory T cells straight into the brain’s delicate learning centers.
- The Type I Interferon Accidental Route: By mapping the molecular cascade, the team identified a highly unexpected signaling pathway driving this cellular hijack: Type I Interferons. These molecules are traditionally recognized as the body’s first-line defensive shield against viral replication, but here they inadvertently act as the executioner of neurogenesis.
- Reversing the Damage: In a major therapeutic triumph, the KCL team introduced an existing therapeutic antibody designed to block Type I Interferon signaling. The intervention successfully reversed the damage, shutting down the recruitment of inflammatory T cells and completely restoring the stem cells’ capacity to regenerate fresh, healthy neurons.
- A Diagnostic Bridge for Long-Syndromes: This discovery provides an invaluable clinical explanation for the persistent cognitive impairments, “brain fog,” and mood disorders reported by patients recovering from aggressive viral infections, navigating major depressive disorders, or entering the early stages of Alzheimer’s disease.
Source: King’s College London
The King’s College London 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 new nerve cells.
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.”
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.
Co-corresponding author Professor Linda S. Klavinskis, Professor of Viral Immunology, King’s College London, added: “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 or restore the brain’s regenerative capacity.”
This research was a collaboration between the Department of Infectious Diseases at the Faculty of Life Sciences & Medicine and the Department of Basic and Clinical Neuroscience at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London.
Funding: 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.
Key Questions Answered:
A: When your body fights off an infection, your immune system releases chemical sirens called cytokines, like TNF-α, to coordinate your defenses. However, if these cytokines remain elevated for too long, they cross over into the brain and invade the hippocampus—the master engine for memory. King’s College London discovered that these inflammatory chemicals completely derail the stem cells meant to grow fresh brain cells, forcing them to stop making neurons and causing the memory decline and cognitive tracking slowdowns we call “brain fog.”
A: This was the biggest surprise of the entire study. Scientists assumed that chronic inflammation simply damaged or killed off neural stem cells. Instead, the research team found that human hippocampal stem cells are active participants in the immune war. When exposed to TNF-α, they actively change their behavior, pivoting into an “immune alert” state. They start operating like immune lookouts, pumping out distress signals to drag destructive inflammatory cells, called T cells, directly into the brain’s learning circuits.
A: Yes, the study uncovered a beautiful potential path for treatment. The researchers isolated a hidden biological route inside the stem cells governed by Type I Interferons, molecules normally used for antiviral defense. By using an existing therapeutic antibody to block this interferon pathway, they managed to trick the stem cells into lowering their immune guard. The treatment successfully stopped the recruitment of harmful T cells and completely restored the brain’s natural capacity to grow fresh, healthy neurons, offering an exciting blueprint for future memory-restoring drugs.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurogenesis research news
Author: Annie Slinn
Source: King’s College London
Contact: Annie Slinn – King’s College London
Image: The image is credited to Neuroscience News
Original Research: Open access.
“TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells” by Tinne A. D. Nissen, Arishma Baig, Sahand Farmand, Daniel T. Rock, Sandra Shibu, Hyunah Lee, Lauren A. O’Neill, Vikki Houghton, Susan John, Linda S. Klavinskis & Sandrine Thuret. Nature Communications
DOI:10.1038/s41467-026-74104-x
Abstract
TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells
Adult hippocampal neurogenesis is essential for learning, memory, and mood regulation, and its disruption is implicated in ageing, neurodegeneration, and mood disorders. However, the mechanisms linking inflammation to adult hippocampal neurogenesis impairment remain unclear.
Here, we identify chronic tumour necrosis factor-alpha signalling as a key driver of neurogenic dysregulation via a previously unrecognised type I interferon autocrine/paracrine loop in human hippocampal progenitor cells.
Using a female-derived human in vitro neurogenesis model, single-cell RNA sequencing, and functional T cell migration assays, we show that tumour necrosis factor-alpha induces a robust type I interferon response in hippocampal progenitor cells, promoting chemokine-mediated and CXC motif chemokine receptor 3-dependent T cell recruitment and suppressing neurogenesis.
This inflammatory signalling cascade drives a fate switch in hippocampal progenitor cells from a neurogenic trajectory towards an immune-defensive phenotype, with critical implications for infectious and inflammatory disease pathogenesis.
These findings uncover a key inflammatory checkpoint regulating human adult hippocampal neurogenesis and highlight potential therapeutic targets to restore neurogenesis in chronic inflammatory states.
