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 21kDa 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.

中文翻译：

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免疫调节蛋白：Annexin-A1转基因自身免疫易感T细胞产生的一种新的焦虑因子

患有自身免疫性疾病的患者更容易患上精神障碍，但这些病理并存背后的特定细胞和分子机制的存在远未完全阐明。通过生成仅在 T 细胞中过度表达 Annexin-A1 的转基因小鼠，以研究其在自身免疫性疾病模型中的影响，我们意外地观察到焦虑程度的增加。Annexin-A1 CD4+ T 细胞的基因芯片鉴定了一种新的焦虑因子，一种大约 21kDa 的小蛋白，由我们命名为 Immuno-moodulin 的基因 2610019F03Rik 编码。针对免疫调节蛋白的中和抗体恢复了 Annexin-A1 转基因小鼠的行为表型，并降低了野生型小鼠的基础焦虑水平；而且，我们还发现，患有强迫症的患者在其外周单核细胞中表现出高水平的 Imood。因此，我们将这种蛋白质鉴定为调节焦虑行为的新型外围决定因素。针对免疫调节蛋白的疗法可能会通过调节免疫系统的功能，而不是直接作用于神经系统，从而导致一种新型的精神障碍治疗。