Universit_ Paris VI - Universit_ Paris VII

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MASTER 2 IMMUNOLOGIE
Send to Secrétariat Pédagogique du M2 d'Immunologie
[email protected]
2 pages maximum
Before June 1st 2016
Internship proposal for Master 2
(Proposition de Stage pour M2)
Academic Year 2016 - 2017
1. Team : administrative affiliation (CNRS, INSERM…) and number of the unit:
INSERM U1151- CNRS UMR 8253 (Institut Necker Enfants Malades, INEM),
Name of the head of laboratory : Pr Xavier Nassif
Name of the responsible of the team : Pr Lucienne Chatenoud - Dr Maria Leite-de-Moraes
Name of the team : Immunoregulation and Immunopathology
Address : Hôpital Necker, Bâtiment Hamburger, 149 rue de Sèvres, 75 015 Paris
Responsible for surpervising the student : Dr Odile Devergne
Tél : 01 44 49 53 87 ; Fax : 01 44 49 06 76 ; and E-mail: [email protected]
2. COURSE ( Parcours)
Immunology
X_ Immunologie approfondie (Basic Immunology)
X_ Physiopathologie de la réponse immune (Immunopathology)
3. Project : title and summary (Thème du stage, titre et Description du sujet) (1 page
maximum in english) :
IL-35, human B lymphocytes and B-cell lymphomas
Interleukin-35 (IL-35) is a heterodimeric of the IL-12 family that we identified, and is
composed of two subunits, EBI3 and p35. EBI3 can also dimerize with another subunit,
p28, to generate IL-27, a cytokine with immunostimulatory or suppressive functions.
Mouse studies have demonstrated that IL-35 is produced by regulatory T cells (Treg cells)
and contributes to their suppressive functions in inflammatory and auto-immune
conditions. Recently, Treg-derived IL-35 was also shown to limit anti-tumor immunity by
promoting T-cell exhaustion and dysfunction through the induction of various inhibitory
receptors such as PD1, TIM3 and LAG3 (Turnis et al, Immunity 2016). Furthermore, IL-35
is expressed by mouse regulatory B cells and regulates immunity during autoimmune and
infectious diseases (Shen et al, Nature 2014 ; Wang et al, Nat Medicine 2014).
Our preliminary data suggest that, in humans, IL-35 is expressed by specific B-cell subsets
and is overexpressed by tumor cells in various forms of aggressive B-cell lymphomas,
notably diffuse large B-cell lymphomas (DLBCL), in both cases in the absence of IL-27.
The project aims at further characterizing the expression profile of IL-35 in human B cells
in in situ and in vitro studies, and assessing its potential suppressive function in in vitro
assays. This study will be perfomed in parallel to an in situ study of IL-35 expression in a
serie of DLBCL cases and correlation with the patient prognosis. This study will allow to
establish the existence of IL-35+ human Breg cells and to evaluate the potential role of IL35 in the development of B-cell lymphomas.
4.
Composition of the team
Number of scientists :
Senior scientists :
Technician-Engineer :
Postdoc :
Total :
.....7.....
.....4....
.....4....
....12....
with HDR* :
.....6.....
Total HDR :
.....6...
Number of students :
Master 2
1° Year of PhD :
2° Year of PhD:
3° Year of PhD :
4° Year of PhD :
Total PhD Students :
…1…
....1....
....1....
..........
..........
....2....
5. Publications (5 most significant during the 4 last years).
Charlot-Rabiega P, Bardel E, Dietrich C, Kastelein RA, Devergne O. Signaling events involved
in interleukin 27 (IL-27)-induced proliferation of human naive CD4+ T cells and B cells. J Biol
Chem 2011, 286:27350-27362
Gonin J, Larousserie F, Bastard C, Picquenot JM, Couturier J, Radford-Weiss I, Dietrich C,
Brousse N, Vacher-Lavenu M-C, Devergne O. Epstein-Barr virus-induced gene 3 (EBI3) : a
novel diagnosis marker in Burkitt lymphoma and diffuse large B-cell lymphoma, PloS One 2011,
6:e24617.
Moreira-Teixeira L, Resende M, Devergne O, Herbeuval J-P, Hermine O, Schneider E, Dy M,
Cordeiro-da-Silva A, Leite-de-Moraes MC. Rapamycin combined with TGF-ß converts human
invariant NKT cells into suppressive Foxp3+ regulatory cells. J Immunol 2012,188:624-631.
Gonin J, Carlotti A, Dietrich C, Audebourg A, Radenen-Bussière B, Caignard A, Avril MF,
Vacher-Lavenu MC, Larousserie F, Devergne O. Expression of IL-27 by tumor cells in invasive
cutaneous and metastatic melanomas. PLoS One 2013, 8:e75694.
Dietrich C, Candon S, Ruemmele FM, Devergne O. A soluble form of IL-27R is a natural IL-27
antagonist. J Immunol 2014, 192:5382-5389 (Editorial in In This Issue section, p4940).
Membership of the Doctoral School (Appartenance à L’Ecole Doctorale)
BioSPC
B2T
 PPATH  Autre : ………
* Habilitation to supervise research