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Immuno-moodulin is Differentially Expressed in T Cells and Plasma in Obsessive-Compulsive Disorder Patients

Blacksell, I. A.; Vismara, M.; Lim, C. M.; Dell'Osso, B.; Pallanti, S.; Hollander, E.; Vendruscolo, M.; D'Addario, C.; Cooper, D.; D'Acquisto, F.

2024-12-20 immunology
10.1101/2024.12.16.628685 bioRxiv
Show abstract

Immuno-moodulin (Imood), a recently discovered protein expressed in T cells, is associated with anxiety-like behavior in mice. However, its mechanism of action in modulating neuroimmune interactions remains unclear. To investigate this problem, we characterized Imood in human blood and immune cells using neutralizing monoclonal antibodies, revealing its nature as an intrinsically disordered protein (IDP) with unique expression patterns. Our findings indicate that Imood is predominantly expressed intracellularly in peripheral blood mononuclear cells (PBMCs), particularly T lymphocytes, but is absent in polymorphonuclear cells. Upon T-cell activation, Imood exhibits distinct mobilization patterns with increased surface expression. Bioinformatics analysis identified a strong propensity for oligomerization and liquid-liquid phase separation. We also found that T cells from patients with Obsessive-Compulsive-Disorder (OCD) displayed significantly elevated surface Imood expression compared to healthy controls, as well as an altered level of Imood polymerization in the plasma. Taken together, these results elucidate the expression patterns and structural properties of Imood in human immune cells, which open new avenues for OCD diagnostics, and prompt further study for understanding the aetiology of OCD and related disorders.

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