Institut thématique Neurosciences, sciences cognitives, neurologie, psychiatrie

Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination. The goal of this study was to compare peripheral blood immune cell populations in recent onset pediatric NT1 subjects (post or non-post 2009-influenza A H1N1 vaccination) to healthy donors. We demonstrated an increased number of central memory CD4+ T cells (CD62L+ CD45RA-) associated to an activated phenotype (increase in CD69 and CD25 expression) in NT1 patients. Percentage and absolute count of regulatory T cells (Tregs) in NT1 patients were increased associated with an activated phenotype (increase in GITR and LAP expression), and of activated memory phenotype. Cytokine production by CD4+ and CD8+ T cells after activation was not modified in NT1 patients. In H1N1 vaccinated NT1 patients, absolute counts of CD3+, CD8+ T cells, and B cells were increased compared to non-vaccinated NT1 patients. These results support a global T cell activation in NT1 patients and thus support a T cell-mediated autoimmune origin of NT1, but do not demonstrate the pathological role of H1N1 prophylactic vaccination. They should prompt further studies of T cells, particularly of Tregs (such as suppression and proliferation antigen specific assays, and also T-cell receptor sequencing), in NT1.

Le modèle de structuration de la recherche et des soins de cancérologie en France constitue un contexte propice au déploiement de la formation à la recherche translationnelle. Favorisant la proximité des équipes de différentes disciplines, cette organisation est consolidée par des actions de soutien spécifiques qui ont pour objectif de renforcer les interfaces, instaurer un dialogue toujours plus efficace entre les acteurs et créer de nouveaux postes répondant aux besoins spécifiques et évolutifs de la recherche sur le cancer. De par la nature de cette pathologie, la multidisciplinarité est une composante indispensable aux recherches portant sur la prévention, le dépistage et le traitement des cancers. Des efforts particuliers sont donc déployés et doivent être poursuivis pour l’amélioration des parcours de formation à la recherche translationnelle qui se caractérise elle‑même par des échanges continus et bidirectionnels entre les disciplines fondamentales et cliniques.

This joint Canada- and France-led Event will provide a forum to explore the new paradigms governing synergies between industry and academia in order to develop new approaches to dementias. The goals of the Third Legacy Event include: 1) Exploring opportunities for research into novel diagnostic, pre-emptive, and therapeutic approaches to dementia (including new models of care, providing a better understanding of the paradigm shift in pharmaceutical research on drug development, and finding innovative ways to engage the medical device and IT industries); 2) Fostering a collective approach to problem–solving through the pooling of resources and the sharing of cohorts, data, and best practices.

International audience