Étude d’un modèle murin transgénique spontané d’encéphalomyélite auto-immune expérimentale : investigation de l’état de la barrière hémo-encéphalique et des différences liées au sexe
The TCR1640 transgenic mice carry a T cell receptor specific for myelin oligodendrocyte glycoprotein peptide 92-106 and develop spontaneous experimental autoimmune encephalomyelitis (EAE). The disease is more prevalent in female mice and most of them develop an EAE with a relapsing-remitting (RR) disease course whereas the majority of the males present a primary progressive (PP)-EAE. This model perfectly reflects disease-related sex differences, heterogeneous disease courses, pathology and immune cell involvement seen in multiple sclerosis. The aim of this project is to study how the pathological burden evolves in spontaneous EAE developed by TCR1640 mice, and to unravel mechanisms behind sex-related difference.  The blood-brain barrier (BBB) permeability and integrity of central nervous tissues from TCR1640 mice was investigated at different phases in the disease, using immunohistochemistry. BBB alterations were found in active phases of the disease, accompanied by CD4+ and FOXP3+ T cell infiltration and endothelium activation. The integrity of the BBB seems to be re-established following remission phase. To investigate disease-related sex differences observed in these mice, an adoptive transfer experiment was performed. Immune cells from TCR1640 were injected in WT mice in different combinations of males or females donor and recipient. We found that recipients injected with male cells developed PP-EAE, whereas recipients injected with females cells developed RR-EAE, regardless of the sex of the recipient animal. Moreover, transcriptomic analysis revealed that gene expression differs in immune cells for males versus females TCR1640 suggesting that RR versus PP disease course is dictated by sex-dependent genes encoded by the immune compartment.
Multiple sclerosis Experimental autoimmune encephalomyelitis Sex-differences Blood brain barrier