Immuno-moodulin: A new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells

Giuseppa Piras, Lorenza Rattazzi, Nikolaos Paschalidis, Silvia Oggero, Giulio Berti, Masahiro Ono, Fabio Bellia, Claudio D'Addario, Bernardo Dell'Osso, Carmine Maria Pariante, Mauro Perretti, Fulvio D'Acquisto

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Abstract

Patients suffering from autoimmune diseases are more susceptible to mental disorders yet, the existence of specific cellular and molecular mechanisms behind the co-morbidity of these pathologies is far from being fully elucidated. By generating transgenic mice overexpressing Annexin-A1 exclusively in T cells to study its impact in models of autoimmune diseases, we made the unpredicted observation of an increased level of anxiety. Gene microarray of Annexin-A1 CD4+ T cells identified a novel anxiogenic factor, a small protein of approximately 21 kDa encoded by the gene 2610019F03Rik which we named Immuno-moodulin. Neutralizing antibodies against Immuno-moodulin reverted the behavioral phenotype of Annexin-A1 transgenic mice and lowered the basal levels of anxiety in wild type mice; moreover, we also found that patients suffering from obsessive compulsive disorders show high levels of Imood in their peripheral mononuclear cells. We thus identify this protein as a novel peripheral determinant that modulates anxiety behavior. Therapies targeting Immuno-moodulin may lead to a new type of treatment for mental disorders through regulation of the functions of the immune system, rather than directly acting on the nervous system.

Original languageEnglish
Pages (from-to)689-702
JournalBrain, behavior, and immunity
Volume87
Early online date29 Feb 2020
DOIs
Publication statusPublished - 1 Jul 2020

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