MeCP2 Regulates the Immune Response During an Autoimmune Challenge

MARIA INÉS ZALOSNIK FIGUEROA; MARIA LAURA BERTOLDI; MARIA CAROLINA FABIO; CLARA N CASTAÑARES; GERMAN ALFREDO ROTH; ALICIA L. DEGANO

Cordoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Argentine Society for Research in Neurosciences

Rett syndrome (RTT) is a category of pervasive developmental disorders caused by mutation of MECP2, a gene that encodes methyl-CpG binding protein 2 (MeCP2), a ubiquitously expressed transcriptional regulator. The main goal of our project is to evaluate the role of altered immunity in the pathogenesis of this disorder. To this end, we evaluated the autoimmune response in the context of the experimental autoimmune encephalomyelitis (EAE). Male MeCP2 WT and MT mice were immunized with MOG 35-55 peptide, scored daily for EAE symptoms, and sacrificed at 12 dpi (acute stage) or at 30 dpi (chronic stage). We found that MT-EAE mice showed an accelerated onset of the disease and more severe clinical scores, accompanied by increased infiltration of lymphocytes in spinal cord. The level of microgliosis (Iba1þ cells) was analyzed by IHC and RT-PCR, and we found significant differences between EAE and control group. To determine the response of immune cells, we restimulated spleen mononuclear cells derived from WT and MT mice with MOG peptide in vitro. MT-EAE group showed increased IFN-c levels in response to MOG in comparison with WT-EAE animals with no differences in the proliferation index. Also, the level of gene expression of TNF-a and IFN-c was significantly increased in spinal cords from MT-EAE animals during chronic stage compared to WT. Our results indicate that MeCP2 has an active role in regulating the immune response and maintaining the neuroimmune homeostasis.