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

TY - JOUR

T1 - Immuno-moodulin

T2 - A new anxiogenic factor produced by Annexin-A1 transgenic autoimmune-prone T cells

AU - Piras, Giuseppa

AU - Rattazzi, Lorenza

AU - Paschalidis, Nikolaos

AU - Oggero, Silvia

AU - Berti, Giulio

AU - Ono, Masahiro

AU - Bellia, Fabio

AU - D'Addario, Claudio

AU - Dell'Osso, Bernardo

AU - Pariante, Carmine Maria

AU - Perretti, Mauro

AU - D'Acquisto, Fulvio

N1 - Copyright © 2020 Elsevier Inc. All rights reserved.

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.bbi.2020.02.015

DO - 10.1016/j.bbi.2020.02.015

M3 - Article

C2 - 32126289

SN - 0889-1591

VL - 87

SP - 689

EP - 702

JO - Brain, behavior, and immunity

JF - Brain, behavior, and immunity

ER -