Le vendredi 13 décembre 2024, Monsieur Glenn VAN HULST, titulaire d’un Master of biomedical sciences (Maastricht University) et d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en Sciences biomédicales et pharmaceutiques, sous la direction de Monsieur Christophe DESMET et de Monsieur Fabrice BUREAU.

Cette épreuve consistera en la défense publique d'une thèse intitulée :  "Unraveling the influence of Interleukin-5 on eosinophil development: contribution to a better understanding of precision therapies for severe eosinophilic asthma". 

Le jury sera composé de :

Bénédicte MACHIELS (Présidente), Catherine MOERMANS (Secrétaire), Fabrice BUREAU, Didier CATALDO, Christophe DESMET, Christoph KLOSE (Univ. Berlin), Bart LAMBRECHTS (UGent), Michel MOUTSCHEN.

Résumé de la thèse

Interleukin-5 (IL-5) is a cytokine almost exclusively devoted to the regulation of eosinophils, a specific type of granulocytes playing detrimental roles in prevalent respiratory diseases such as asthma. IL-5 is thought to be essential to eosinophil expansion, maturation, survival and activation. Consequently, IL-5 is now the target of monoclonal antibodies for treating eosinophil-associated disorders, but its exact function and effects on the development and regulation of eosinophils are poorly described. In this work, we used a translational approach to resolve the effects of IL-5 on the eosinophil lineage. Using single-cell proteomics and transcriptomics, we resolved and reconciled eosinophilopoiesis in human and mice and showed that IL-5 is an essential rheostat of the transit amplification, but not the maturation, of the eosinophil lineage. In addition, we showed that residual eosinophils that develop in IL-5-depleted conditions in human and mice harbor largely unaltered gene expression programs, further supporting a limited role of IL-5 in eosinophil maturation. Altogether, this work contributes to a better understanding of the mechanisms of action of the currently widespread used anti-IL-5 biological therapies and of the regulation of eosinophil numbers in health and disease.