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Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2018
Renseignements relatifs à l’Unité de Recherche :
Label et intitulé : Institut Necker Enfants Malades ; Université Paris Descartes, INSERM U1151
Nom et prénom du Directeur : Xavier Nassif
Téléphone :
Télécopie :
Courriel: [email protected]
Renseignements relatifs à l’Equipe :
Nom de l’Equipe d’Accueil : Equipe 13 « Lymphopoïèse et progéniteurs hématopoïétiques
immunorégulateurs »
Nom et prénom du responsable : Sophie Ezine
Qualité du responsable : DR2 INSERM
Téléphone :
Télécopie :
Courriel : [email protected]
Renseignements relatifs au sujet de thèse :
Nom et prénom du Directeur de thèse (HDR) : Marie Cherrier
Qualité : CR1 INSERM
Téléphone :
01 72 60 64 96
Télécopie :
Courriel : [email protected]
Titre du sujet proposé :
(En français) Régulation de l’homéostasie des ILC par les cellules T
(En anglais) T cell mediated regulation of ILC homeostasis
Département (cocher le département correspondant au sujet de thèse qui n’est pas obligatoirement le
vôtre) :
 Biologie Cellulaire et moléculaire, Physiologie et Physiopathologie
 Immunologie
 Développement Génétique Neurobiologie et Vieillissement
 Infectiologie, Microbiologie
Summary (5 lines maximum) :
Intestinal homeostasis relies on a fine equilibrium that is broken during chronic and acute inflammatory
diseases. Both Innate lymphoid cells (ILCs) and T cells participate in the maintenance of this equilibrium
through their ability to fight against pathogens and to induce tolerance towards the gut microbiota. A
constant and dynamic dialogue between T cells and ILCs is therefore essential. The aim of this project is
to describe the crosstalk between T cells and ILCs, identify its underlying mechanisms and determine the
role of the microbiota in this process.
Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2087
(L’ensemble de cette fiche ne doit pas dépasser 1 page)
Nom, prénom du directeur de l'unité de recherche : Xavier Nassif
Numéro de l'unité de recherche (et établissement de rattachement) : INSERM U1151 Université Paris
Descartes
Nom, prénom du responsable de l'équipe d'accueil (EAD) : Sophie Ezine
Nom, prénom du directeur de thèse : Marie Cherrier
Titre du sujet de thèse proposé : T cell mediated regulation of ILC homeostasis
(en anglais)
Citer 5 mots clés : Homeostasis, T cells, Innate Lymphoid cells, Micro-environment, Microbiota
(key words)
Candidat pressenti :

OUI

NON
Contenu scientifique du programme de la thèse (en anglais)
Both T cells and ILCs are involved in intestinal homeostasis and immunity. Therefore a constant dialogue
between T cells and ILCs is necessary to coordinate optimal immune responses at the steady state and
during infections. It has been shown that ILCs have the capacity to promote and/or to modulate T cell
responses towards microbiota derived antigens.
Whether and how T cells can in turn shape the composition and the activity of ILCs still needs to be
investigated.
We showed that constitutive T cell deficiency results in strikingly different functional and homeostatic
outcomes for ILCs depending on the tissue in which they reside. While there is a significant shift towards
type 2 immunity in ILCs residing in secondary lymphoid organs such as peripheral and mesenteric lymph
nodes, IL-22 producing NKp46+ ILCs as well as ILCs residing in cryptopatches and Isolated Lymphoid
Follicles are increased in the lamina propria of the small intestine of T cell deficient mice.
Adoptive transfers of T cells and antibiotic treatment confirmed that distinct mechanisms and microenvironmental cues account for the striking differences observed between lymphoid tissue resident and
gut resident ILCs of T cell deficient mice. Our objective is to determine the role of commensal bacteria,
tissue resident and migratory dendritic cells as well as lymphoid tissue stromal cells in the complex
network of interactions underlying the cross talk between ILCs and T cells.
Our work will be the first one to address the diversity of actors and mechanisms involved in the complex
and multi-layered regulation of ILC homeostasis by adaptive immunity. Our investigations will clarify the
respective role of T cells, environmental cues such as commensal bacteria and food derived antigens and
sensors of these cues at the steady state. This should highlight new regulatory mechanisms through which
ILCs are maintained as quiescent tissue resident sentinels and prevented from participating in and/or
initiating chronic tissue inflammation. Our work is therefore of particular interest for future pre-clinical
studies since it will provide the basic knowledge that is necessary for the development of new therapeutic
strategies to treat conditions such as intestinal inflammation, asthma and food allergies.
Indiquez les cinq meilleures publications récentes de l’équipe :
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Cherrier M. [Innate lymphoid cells: new players of the mucosal immune response]. Med Sci (Paris). 2014
Mar;30(3):280-8.
Cherrier M , Cording S, Medvedovic J, , Eberl G. Development and regulation of RORγt(+) innate
lymphoid cells. FEBS Lett. 2014 Nov 17;588(22):4176-81.
Marie Cherrier, Shinichiro Sawa, Gérard Eberl. Notch, Id2 and ROR t sequentially orchestrate the
differentiation of fetal LTi cells. J Exp Med. 2012 Apr 9;209(4):729-40.
Shinichiro Sawa, Marie Cherrier, Matthias Lochner, Naoko Satoh-Takayama, Hans Jörg Fehling, Francina
Langa, James P. Di Santo, Gérard Eberl. Lineage Relationship Analysis of ROR t+ Innate Lymphoid
Cells. Science. September 2010. Vol. 330 no. 6004 pp. 665-669.