Le mercredi 19 juin 2024, Madame Caroline WATHIEU, titulaire d’un Master en sciences biomédicales à finalité approfondie 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 Alain CHARIOT.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "A role for tRNA modifications in tuft cell differentiation and in the immune response to intestinal helminths". 

Le jury sera composé de :

Bernard ROGISTER (Président), Pierre CLOSE (Secrétaire), Alain CHARIOT, Benjamin DEWALS, Irah KING (McGill University), Laurent NGUYEN, Geert VAN LOO (UGent).

Résumé de la thèse :

Intestinal tuft cells are critical in anti-helminth immunity by producing IL-25, which triggers IL-13 secretion by activated group 2 innate lymphoid cells (ILC2s) to expand both goblet and tuft cells. We show that epithelial Elp3, a tRNA-modifying enzyme, promotes tuft cell differentiation and is consequently critical for IL-25 production, ILC2 activation, goblet cell expansion and control of N. brasiliensis infection in mice. Elp3 is essential for the IL-13-dependent induction of some glycolytic enzymes such as Hexokinase 1 and Aldolase A and consequently links specific metabolic pathways to tuft cell differentiation. Importantly, loss of epithelial Elp3 in the intestine blocks the translation of Nprl2, a mTORC1 inhibitor, which consequently enhances mTORC1 activation and stabilizes Atf4 in both transit amplifying and progenitor cells. Likewise, Atf4 overexpression in mouse intestinal epithelium blocks tuft cell differentiation and impairs the control of intestinal helminth infection. Collectively, our data define Atf4 as a negative regulator of tuft cell differentiation and provide insights into mechanisms through which some tRNA modifications promote a type 2 immune response to parasites in the intestine.