Rôles du système de l'interleukine-1β dans l'encéphalite auto-immune expérimentale, un modèle de sclérose en plaques
|Abstract:||Interleukin-1b (IL-1b) is an inflammatory cytokine that actively participates in sterile and pathogen-dependant immune responses. Given its mighty inflammatory potential, regulatory defects in the IL-1b system may participate to the pathophysiology of some diseases and syndromes. One such plausible pathology is multiple sclerosis, an autoimmune disease characterised by the presence of demyelinating plaques in the central nervous system (CNS), neurodegeneration as well as motor and cognitive defects. The main objective of this thesis was to study the contribution of the IL-1b system in a mouse model of the disease, experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of the human pathology. The results of these experiments were incorporated into two scientific studies included in this thesis. The first study allowed us to confirm the importance of IL-1b and its receptor, IL-1R1, in the development of paralysis in EAE. We were able to identify myeloid cells (neutrophils, monocytes and macrophages) as the principal sources of IL-1b in EAE. The study also allowed us to examine the ignificance of the effects of IL-1b on CNS endothelial cells. In the second study, we showed that the production of IL-1b by inflammatory monocytes was crucial for their migration into the CNS parenchyma. Once inside the CNS, monocytes acquire an antigen-presenting cell phenotype and activate CD4+ T lymphocytes in an IL-1b-dependant manner. This activation gives an highly inflammatory and neurotoxic phenotype to CD4+ T cells. Overall, the results presented in this thesis show that the IL-1b system regulates several cellular mechanisms implicated in the development and exacerbation of CNS autoimmunity. This work and the work of others justify a more exhaustive study of the molecular signals induced by IL-1b in CNS endothelial cells and T lymphocytes, both in EAE and multiple sclerosis. These studies could lead to the identification of therapeutic targets that would only impact the negative and pathogenic effects mediated by IL-1b.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||7 May 2018|
|Collection:||Thèses et mémoires|
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