Integrative Biology of Human Dendritic Cells and T Cells Integrative Biology of Human Dendritic Cells and T Cells

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

INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1 Integrative Biology of Human Dendritic Cells and T Cells Integrative Biology of Human Dendritic Cells and T Cells

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 2018

Alculumbre SG, Saint-André V, Di Domizio J, Vargas P, Sirven P, Bost P, Maurin M, Maiuri P, Wery M, Roman MS, Savey L, Touzot M, Terrier B, Saadoun D, Conrad C, Gilliet M, Morillon A, Soumelis V (2018 Jan 1) Diversification of human plasmacytoid predendritic cells in response to a single stimulus Nature Immunology : 19(1) : 63-75 : DOI : 10.1038/s41590-017-0012-z

INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2 Integrative Biology of Human Dendritic Cells and T Cells Integrative Biology of Human Dendritic Cells and T Cells

Year of publication 2015

Cristina Ghirelli, Fabien Reyal, Marine Jeanmougin, Raphaël Zollinger, Philémon Sirven, Paula Michea, Christophe Caux, Nathalie Bendriss-Vermare, Marie-Hélène Donnadieu, Martial Caly, Virginie Fourchotte, Anne Vincent-Salomon, Brigitte Sigal-Zafrani, Xavier Sastre-Garau, Vassili Soumelis (2015 May 16) Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes. Cancer research : 2775-87 : DOI : 10.1158/0008-5472.CAN-14-2386

Antonio Cappuccio, Raphaël Zollinger, Mirjam Schenk, Aleksandra Walczak, Nicolas Servant, Emmanuel Barillot, Philippe Hupé, Robert L Modlin, Vassili Soumelis (2015 Apr 21) Combinatorial code governing cellular responses to complex stimuli. Nature communications : 6847 : DOI : 10.1038/ncomms7847

Year of publication 2014

Maxime Touzot, Maximilien Grandclaudon, Antonio Cappuccio, Takeshi Satoh, Carolina Martinez- Cingolani, Nicolas Servant, Nicolas Manel, Vassili Soumelis (2014 May 29) Combinatorial flexibility of cytokine function during human T helper cell differentiation. Nature communications : 3987 : DOI : 10.1038/ncomms4987

INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3