Summary: Researchers report that people with obsessive-compulsive disorder (OCD) show roughly six times higher expression of a newly identified protein, Immuno-moodulin (Imood), in their lymphocytes compared with people without the disorder. In mouse models, blocking Imood with a neutralising antibody reduced behaviors reminiscent of OCD and anxiety within days of treatment.
Source: Queen Mary University of London
Researchers at Queen Mary University of London and the University of Roehampton in London have identified elevated levels of a protein they call Immuno-moodulin (Imood) in immune cells from people with obsessive-compulsive disorder.
The team observed that mice engineered to express high levels of Imood in T cells displayed behaviours commonly associated with stress and anxiety, including excessive grooming and repetitive digging. When those mice received an antibody that neutralised Imood, the anxious behaviours subsided and activity patterns returned to typical levels within a few days.
These findings prompted the researchers to file a patent application for the antibody and to begin collaborative work with a pharmaceutical company to explore the development of a potential human therapy.
“There is growing evidence that the immune system is central to the development of many mental health conditions,” said Professor Fulvio D’Acquisto, professor of immunology at the University of Roehampton and honorary professor of immunopharmacology at Queen Mary University of London, who led the study. “Patients with autoimmune diseases frequently have higher rates of anxiety, depression and obsessive-compulsive disorder. Our results challenge the conventional view that these conditions arise solely from nervous system dysfunction, and point toward immune-driven mechanisms as a contributing factor.”
Professor D’Acquisto and colleagues published their work in the journal Brain, Behavior, and Immunity. The team initially encountered Imood serendipitously while investigating Annexin-A1, a protein implicated in autoimmune diseases such as multiple sclerosis and lupus. In generating transgenic mice that overexpress Annexin-A1 in T cells, they unexpectedly observed increased anxiety-like behaviour. Gene expression analysis of those T cells revealed a single gene with markedly elevated activity; that gene produces the 21 kDa protein now named Immuno-moodulin.
Administering an antibody that blocks Imood to the anxious mice reversed the behavioural changes within days. To explore relevance to humans, the researchers analysed immune cells from 23 people diagnosed with OCD and 20 healthy volunteers. Imood levels in peripheral blood mononuclear cells were approximately six times higher in the OCD group than in controls.
Other independent studies have also suggested Imood may play a role in neurodevelopmental or psychiatric conditions such as attention-deficit/hyperactivity disorder, supporting the idea that this protein could have broader relevance to brain-related symptoms that co-occur with immune dysregulation.
Professor D’Acquisto emphasises that Imood is unlikely to act like a classical neurotransmitter by directly altering neuronal chemistry. Instead, the protein may influence gene networks within brain cells or modify peripheral signals that indirectly alter brain function. “We still need to determine exactly how Imood affects neural circuits and behaviour,” he said. “Larger patient studies and further mechanistic work are required to confirm our initial findings and to map the pathways involved.”
Meanwhile, Professor D’Acquisto and Dr Dianne Cooper, senior lecturer at Queen Mary University of London, are collaborating with the biopharmaceutical company UCB to develop human-compatible antibodies targeting Imood and to test how such therapies might treat mental health conditions linked to immune activity.
“Although this work is at an early stage, therapeutic antibodies that target immune-derived regulators of behaviour could offer an alternative to traditional small-molecule psychiatric drugs, potentially reducing off-target effects and improving safety,” Professor D’Acquisto said. He estimates that, if development proceeds successfully, it could take up to five years before a candidate treatment reaches clinical trials.
About this neuroscience research article
Source:
Queen Mary University of London
Media contacts:
Jo Kelly – Queen Mary University of London
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Original Research: Closed access
“Immuno-moodulin: A new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells” by Fulvio D’Acquisto et al., published in Brain, Behavior and Immunity. DOI: 10.1016/j.bbi.2020.02.015.
Abstract
Immuno-moodulin: A new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells
Patients with autoimmune disorders are more likely to develop mental health conditions, yet the cellular and molecular mechanisms linking these pathologies remain poorly understood. While generating transgenic mice that overexpress Annexin-A1 specifically in T cells to study autoimmune disease mechanisms, the researchers observed an unexpected increase in anxiety-like behaviour. Gene expression profiling of CD4+ T cells from these mice identified a novel anxiogenic factor, a roughly 21 kDa protein encoded by the gene 2610019F03Rik, which the authors have named Immuno-moodulin. Neutralising antibodies against Imood reversed the anxious behavioural phenotype of Annexin-A1 transgenic mice and reduced baseline anxiety in wild-type mice. The study also detected elevated Imood levels in peripheral mononuclear cells from patients with obsessive-compulsive disorder. These results identify Imood as a peripheral immune-derived regulator of anxiety-like behaviour and suggest that therapies targeting Imood could provide a new approach to treating mental disorders by modulating immune system function rather than acting directly on the central nervous system.
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