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Transcript
Integrative Biology of Human Dendritic Cells and T Cells
U932 – Immunity and Cancer
Vassili Soumelis
Chef d'équipe
[email protected]
Tel: +33 1 44 32 42 27
Living systems are open system organized in a
hierarchical manner, from whole organisms, to tissues,
and cells. Basic characteristics are shared by all
hierarchical levels and include the ability of a system to
adjust to changes in its environment. Our general aim is
to understand the reciprocal interactions between
immune cell state/behavior and their environment in a
global and integrated manner. We use dendritic cells and
T cells as preferred cellular systems, but our conclusions
may apply to various types of cells, and living systems in
general. Our research is organized in three
interconnected programs.
Program 1: Systems and integrative biology of human immune cells
Among the diversity of immune cell types, dendritic cells (DCs) are central to the immune
response and have the unique capacity to link innate and adaptive immunity. Their function is
tightly linked to their ability to integrate multiple signals from a complex inflammatory
environment and to translate these signals into the appropriate innate and adaptive (T cell)
responses. Our specific aims are to understand how DC integrate these signals and how such
innate DC priming will affect T cell activation and polarization. These questions are addressed in
physiological and/or pathological settings.
Program 2: Global analysis of human tissue inflammation and tumor
microenvironment
Each type of inflammation (infection, cancer, allergy etc…) is characterized by intercellular
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1
Integrative Biology of Human Dendritic Cells and T Cells
U932 – Immunity and Cancer
communication networks that globally explain and drive the pathogenic process. Each of these
networks is developed through a dysregulation of physiological processes. Our global aim is to
reconstruct such networks by focusing on individual components (cells, soluble factors,
membrane receptors), or by integrating multiple components using systems biology and
modeling.
Program 3: Biology of human TSLP
The cytokine TSLP is produced by epithelial cells, and targets DC in order to modulate their
behavior. We are studying the role of TSLP in various types of skin inflammation, and tumors.
This program is highly interconnected with programs 1 and 2, since we aim at exploring TSLP
biology in various inflammatory using systems biology approaches.contexts
Figure 1 : Intercellular communication cascades in primary immune response
Dendritic cells (DC) integrate a diversity of signals from inflamed tissue, and subsequently induce the
differentiation of naïve CD4 T cells into T helper effector cells. For each cell interaction, multiple input stimuli
are integrated and multiple output signals are delivered. Such cascades can be studied by focusing on
individual components or in a multiparametric manner.
Work environment and general approaches
The research is conducted by an international team of 10-12 people with a diversity of expertise
in a collaborative environment. We work exclusively in the human system, mostly with primary
cells and tissue, with a constant concern of recreating conditions that mimic the in situ and in
vivo settings. We use a diversity of approaches ranging from cellular immunology, cell
purification and culture, cellular and molecular biology, biochemistry, computational biology and
modeling. We established specific interfaces with the departments of cell biology and
bioinformatics/systems biology. We also have strong interactions with the Curie hospital.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2
Integrative Biology of Human Dendritic Cells and T Cells
U932 – Immunity and Cancer
Key publications
Year of publication 2012
Sofia I Bogiatzi, Maude Guillot-Delost, Antonio Cappuccio, Jean-Christophe Bichet, Olfa
Chouchane-Mlik, Marie-Hélène Donnadieu, Emmanuel Barillot, Philippe Hupé, Katerina Chlichlia,
Eleni I Efremidou, Selim Aractingi, Olivier Bayrou, Vassili Soumelis (2012 Mar 11)
Multiple-checkpoint inhibition of thymic stromal lymphopoietin-induced TH2
response by TH17-related cytokines.
The Journal of allergy and clinical immunology : 233-40.e5 : DOI : 10.1016/j.jaci.2012.04.038
Year of publication 2011
Maria-Isabel Fernandez, Mélina L Heuzé, Carolina Martinez-Cingolani, Elisabetta Volpe, MarieHelene Donnadieu, Matthieu Piel, Bernhard Homey, Ana-Maria Lennon-Duménil, Vassili Soumelis
(2011 Jul 19)
The human cytokine TSLP triggers a cell-autonomous dendritic cell migration in
confined environments.
Blood : 3862-9 : DOI : 10.1182/blood-2010-12-323089
Year of publication 2010
Yves Lepelletier, Raphaël Zollinger, Cristina Ghirelli, Françoise Raynaud, Réda Hadj-Slimane,
Antonio Cappuccio, Olivier Hermine, Yong-Jun Liu, Vassili Soumelis (2010 Jun 30)
Toll-like receptor control of glucocorticoid-induced apoptosis in human
plasmacytoid predendritic cells (pDCs).
Blood : 3389-97 : DOI : 10.1182/blood-2010-05-282913
Cristina Ghirelli, Raphaël Zollinger, Vassili Soumelis (2010 Apr 9)
Systematic cytokine receptor profiling reveals GM-CSF as a novel TLRindependent activator of human plasmacytoid predendritic cells.
Blood : 5037-40 : DOI : 10.1182/blood-2010-01-266932
Year of publication 2009
Elisabetta Volpe, Maxime Touzot, Nicolas Servant, Marie-Annick Marloie-Provost, Philippe Hupé,
Emmanuel Barillot, Vassili Soumelis (2009 Aug 24)
Multiparametric analysis of cytokine-driven human Th17 differentiation reveals
a differential regulation of IL-17 and IL-22 production.
Blood : 3610-4 : DOI : 10.1182/blood-2009-05-223768
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3
Integrative Biology of Human Dendritic Cells and T Cells
U932 – Immunity and Cancer
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 4