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/. Résumé and . Abstract,

, Les maladies auto-immunes résultent d'un dysfonctionnement du système immunitaire

. L'étiologie-de-la-pathologie-reste-souvent-inconnue, Dans l'HAI, une principale caractéristique histologique est la présence d'un infiltrat lymphoplasmocytaire formant une hépatite d'interface dommageable. Dans cette maladie, nous avons d'abord pu mettre en évidence une corrélation positive entre l'expression d'APRIL et l'infiltration des PC dans les espaces portes. In vitro, nous avons observé une survie augmentée des PC du foie en présence d'APRIL. La corticothérapie communément prise par les patients HAI ne cible pas directement les PC. Cependant, nous avons remarqué une réduction simultanée de la densité de PC et de l'expression d'APRIL. Ainsi, cette étude étend le rôle de facteur de survie d'APRIL aux PC du foie dans l'HAI. Les rechutes sont fréquentes après arrêt du traitement, nous indiquant que les cellules pathogènes sont épargnées par la thérapie. Nos résultats montrent que le ciblage d'APRIL pourrait être précieux dans l'HAI. Propre de son rôle sur les PC, APRIL a été ciblée avec succès dans plusieurs maladies auto-immunes. Outre ces succès, un essai clinique visant à bloquer APRIL dans la SEP à malheureusement conduit à une exacerbation inattendue de la maladie. Nous avons été capables de montrer qu'APRIL cible un nouveau type cellulaire dans le système nerveux central, les astrocytes. La fixation d'APRIL à la surface des astrocytes dépend d'un nouveau partenaire de liaison, exprimé par ces derniers, les chondroïtines sulfates protéoglycans. Cette interaction induit la production de la cytokine anti-inflammatoire IL-10, Ce projet de thèse s'est focalisé sur la molécule « a proliferation inducing ligand » (APRIL), facteur de survie des plasmocytes (PC) produisant les anticorps, dans l'hépatite auto-immune (HAI) et la sclérose en plaques (SEP)

. Finalement, après injection d'APRIL recombinante dans ce modèle murin, une réduction de la sévérité de la maladie a été observée, Globalement, nous avons identifié APRIL comme une molécule à double rôle dans les maladies auto-immunes

. Mots-clés, Auto-immunité, Sclérose en plaques (SEP), hépatite auto-immune (HAI)