Integrative Biology of Human Dendritic Cells and T Cells

Vassili

Vassili Soumelis Chef d'équipe Tel:

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 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.
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.

 

Key publications

Year of publication 2017

Sylvain Thierry, Wael Jdey, Solana Alculumbre, Vassili Soumelis, Patricia Noguiez-Hellin, Marie Dutreix (2017 Sep 27)

The DNA repair inhibitor Dbait is specific for malignant hematologic cells in blood.

Molecular cancer therapeutics : DOI : molcanther.0405.2017
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis (2017 Apr 22)

TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand.

The Journal of experimental medicine : 1529-1546 : DOI : 10.1084/jem.20150402

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, Marie-Helene 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 TLR-independent activator of human plasmacytoid predendritic cells.

Blood : 5037-40 : DOI : 10.1182/blood-2010-01-266932
All publications