Défense de thèse

Soutenance de thèse de Dawei CHEN


Infos

Dates
26 octobre 2022
Lieu
Faculté de Médecine - Amphithéâtre Léon Frédéricq
Sart Tilman - Tour GIGA B34, +5
4000 Liège
Horaires
17h00

Le mercredi 26 octobre 2022, Monsieur Dawei CHEN subira l'examen en vue de l'obtention du grade académique de Docteur en Sciences biomédicales et pharmaceutiques sous la direction de Monsieur Alain CHARIOT.

Cette épreuve consistera en la défense publique d'un mémoire intitulé :

"Elp3 links tRNA modifications to macrophage polarization"

Macrophage polarization is a process through which macrophages acquire distinct effector states to carry out multiple and sometimes opposite functions. WeMacrophage polarization is a process through which macrophages acquire distinct effector states to carry out multiple and sometimes opposite functions. We show here that the tRNA-modifying enzyme Elp3 is downregulated by classical M1-activating signals in macrophages. Elp3 expression in myeloid cells promotes FoxO1 phosphorylation by M1-activating signals. Elp3 thereby limits the production of pro-inflammatory cytokines and attenuates experimental colitis in mice. In contrast, alternative M2-activating signals upregulate Elp3 expression through a PI3K and STAT6-dependent signaling pathway. The transcriptomic and metabolic reprogramming linked to M2 macrophage polarization critically relies on Elp3, at least through the translation of the mitochondrial ribosome large subunits Mrlp3, Mrlp13 and Mrpl47. Elp3 expression promotes both STAT6 and mTORC2 activation and is critical for the IL-4-dependent induction of M2 markers in macrophages. Mechanistically, Elp3 is required for mTORC2 activation, at least through the production of Ric8b. Moreover, Elp3 expression in myeloid cells promotes Wnt-driven tumor initiation in the intestine by maintaining a pool of tumor-associated macrophages. Therefore, Elp3 differentially regulates M1 and M2 macrophage polarization to control intestinal inflammation while promoting tumor development.  show here that the tRNA-modifying enzyme Elp3 is downregulated by classical M1-activating signals in macrophages. Elp3 expression in myeloid cells promotes FoxO1 phosphorylation by M1-activating signals. Elp3 thereby limits the production of pro-inflammatory cytokines and attenuates experimental colitis in mice. In contrast, alternative M2-activating signals upregulate Elp3 expression through a PI3K and STAT6-dependent signaling pathway. The transcriptomic and metabolic reprogramming linked to M2 macrophage polarization critically relies on Elp3, at least through the translation of the mitochondrial ribosome large subunits Mrlp3, Mrlp13 and Mrpl47. Elp3 expression promotes both STAT6 and mTORC2 activation and is critical for the IL-4-dependent induction of M2 markers in macrophages. Mechanistically, Elp3 is required for mTORC2 activation, at least through the production of Ric8b. Moreover, Elp3 expression in myeloid cells promotes Wnt-driven tumor initiation in the intestine by maintaining a pool of tumor-associated macrophages. Therefore, Elp3 differentially regulates M1 and M2 macrophage polarization to control intestinal inflammation while promoting tumor development. 

 

 

Le Jury sera composé de :

Bernard ROGISTER (Président), Pierre CLOSE (Secrétaire), alain CHARIOT, Emmanuel DEJARDIN, Christophe DESMET, Laurent NGUYEN, Jan VAN DEN BOSCHE(Amsterdam UMC, Pays-Bas), G. VAN LOO (UGent)

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