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<dc:title xml:lang="fr">Rôle des éosinophiles et des cellules lymphoïdes innées dans l'asthme</dc:title>
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<dcterms:abstract xml:lang="fr">Dans la première partie de cette thèse, nous avons cherché à déterminer le rôle de l’éosinophile circulant dans l’asthme par une approche transcriptomique. Nos résultats suggèrent que l’éosinophile recruté sur un site inflammatoire présente des fonctions immunomodulatrices, importantes dans la réparation tissulaire et le retour à l’homéostasie. Dans la deuxième partie de cette thèse, nous avons étudié le rôle des cellules NK et des cellules lymphoïdes innées de type 2 (ILC2) dans l’inflammation asthmatique. Les cellules NK circulantes sont fortement activées dans l’asthme sévère et ont la capacité d’induire l’apoptose d’éosinophiles autologues in vitro. La PGD2 induit la production d’IL-13 par les ILC2 en synergie avec les cytokines épithéliales IL-25 et IL-33. Enfin, ces fonctions sont régulées par la LXA4. En conclusion, notre travail de thèse met en lumière de nouveaux rôles pour l’éosinophile et les cellules lymphoïdes innées dans l’immunopathologie de l’asthme.</dcterms:abstract>
<dcterms:abstract xml:lang="en">In the first part of the thesis, we adopted a transcriptomic-based approach to investigate the activation state of circulating eosinophils in patients with asthma and other unrelated hypereosinophilic diseases. Taken together, our results, which suggest that esoinophils, recruited to inflammatory sites exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis. In the second part of the thesis, we investigated the role of NK cells and type 2 innate lymphoid cells (ILC2) in asthma inflammation. Circulating NK cells are highly activated in severe asthma and promote apoptosis of autologous eosinophils in vitro. ILC2 generate interleukin-13 in response to prostaglandin D2 alone and in a synergistic manner with the airway epithelial cytokines IL-25 and IL-33. Finally, these functions are regulated by lipoxine A4. In conclusion, this thesis highlights new roles for eosinophils and innate lymphoid cells in asthma immunopathology.</dcterms:abstract>
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