Université de Liège Réseau des Bibliothèques

BICTEL/e - ULg
Serveur institutionnel des thèses de doctorat



Nouvelles thèses
dans BICTEL/e - ULg
  • Kreusch, Marie - Graded-commutative nonassociative algebras: higher octonions and Krichever-Novikov superalgebras; their structures, combinatorics and non-trivial cocycles.
  • Simon, Ronnie Ernst - Lattice dynamics in antimony and tellurium based phase-change materials
  • Belleflamme, Alexandre - Detection of past and future atmospheric circulation changes over the North Atlantic region with the help of an automatic circulation type classification
Présentation Recherche thèse Dépôt thèse Accès
gestionnaires
 
Page de résumé pour ULgetd-09112012-120053

Auteur : Condé, Claude
E-mail de l'auteur : Claude.Conde@ulg.ac.be
URN : ULgetd-09112012-120053
Langue : Anglais/English
Titre : Downmodulator role of SHIP-1 in NOD2 signaling
Intitulé du diplôme : Doctorat en sciences
Département : FS - Département des sciences de la vie
Jury :
Nom : Titre :
Chariot, Alain Membre du jury/Committee Member
Desmet, Christophe Membre du jury/Committee Member
Erneux, Christophe Membre du jury/Committee Member
Kufer, Thomas Membre du jury/Committee Member
Struman, Ingrid Membre du jury/Committee Member
Galleni, Moreno Président du jury/Committee Chair
Gloire, Geoffrey Promoteur/Director
Piette, Jacques Promoteur/Director
Mots-clés :
  • XIAP
  • inositol phosphatase
  • NOD2
  • innate immunity/immunité innée
Date de soutenance : 2012-09-21
Type d'accès : Restreint/Intranet
Résumé :

Innate immunity constitutes the first line of host defence against pathogens. It activates inflammation and initial antimicrobial responses prior to the onset of adaptive immunity. Recognition of invading pathogens is a crucial mechanism that relies on recognition of pathogen-associated molecular patterns (PAMPs) by patterns recognition receptors (PRRs). The PRR armada is composed of the membrane-associated toll-like receptors (TLRs) that sense pathogens at cell surface and within the endosomes whereas the cytosolic NOD-like receptors (NLRs) guard the intracellular compartment. NLRs, such as NOD1 and NOD2, are able to induce cytokines, chemokines and antimicrobial peptides production by activating the transcription factor nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Essential role for NOD2 in immunity is highlighted by the fact that mutations in the NOD2 gene are associated with increased risk to develop Crohn’s disease, a chronic inflammatory bowel disease.

SHIP-1 is an SH2-containing inositol 5’-phosphatase principally expressed by hematopoietic cells. Over the past decade, SHIP-1 has been described as an important regulator of immune functions. For instance, SHIP-1 downregulates B cells activation and mast cells degranulation. Strikingly, SHIP-1 is a downmodulator of TLRs signaling. Indeed, SHIP-1 KO macrophages exhibit an increased cytokines production in response to TLR4 triggering and produce more interferon β in response to TLR3 activation than their WT counterpart. The inability of SHIP-1-deficient mice to control TLR activation has a dramatic consequence, as these mice fail to develop an endotoxin tolerance.

Considering the similarity of TLRs and NLRs signaling pathways, this work has investigated the function of SHIP-1 in the negative regulation of the NLR receptors, i.e. NOD1 and NOD2. We have established that SHIP-1 downregulates both NOD1 and NOD2-induced NF-κB activation. This property relies on its interaction with XIAP. Indeed, we have observed that XIAP is an essential mediator of the NOD1 and NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Mechanistically, we defined that, upon NOD2 activation, SHIP-1 interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling.

Autre version :
Fichiers :
Nom du fichier Taille Temps de chargement évalué (HH:MI:SS)
Modem 56K ADSL
[Restreint/Intranet] These_Claude_Conde.pdf 155.91 Kb 00:00:22 < 00:00:01
Fichiers accessibles par l'Internet [Public/Internet] ou que par l'Intranet [Restreint/Intranet].

Bien que le maximum ait été fait pour que les droits des ayants-droits soient respectés, si un de ceux-ci constatait qu'une oeuvre sur laquelle il a des droits a été utilisée dans BICTEL/e ULg sans son autorisation explicite, il est invité à prendre contact le plus rapidement possible avec la Direction du Réseau des Bibliothèques.


Parcourir BICTEL/e par Auteur|Département | Rechercher dans BICTEL/e


© Réseau des Bibliothèques de l'ULg, Grande traverse, 12 B37 4000 LIEGE