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A Quantitative Multivariate Model of Human Dendritic Cell-T Helper Cell Communication

50 Pages Posted: 18 Mar 2019 Sneak Peek Status: Published

See all articles by Maximilien Grandclaudon

Maximilien Grandclaudon

PSL Research University - Centre de Recherche

Marie Perrot-Dockès

University of Paris-Saclay - UMR MIA-Paris

Coline Trichot

PSL Research University - Centre de Recherche

Omar Mostafa-Abouzid

PSL Research University - Centre de Recherche

Wassim Abou-Jaoudé

École Normale Supérieure - PSL Research University - Computational Systems Biology Team

Frédérique Berger

PSL Research University - Centre de Recherche

Philippe Hupé

PSL Research University - Centre de Recherche

Denis Thieffry

École Normale Supérieure - PSL Research University - Computational Systems Biology Team

Laure Sansonnet

University of Paris-Saclay - UMR MIA-Paris

Julien Chiquet

University of Paris-Saclay - UMR MIA-Paris

Céline Levy-Leduc

University of Paris-Saclay - UMR MIA-Paris

Vassili Soumelis

Université Paris VI Pierre et Marie Curie - Research Center

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Abstract

Cell-cell communication involves a large number of molecular signals that function as words of a complex language, the grammar of which remaining mostly unknown. Here, we describe an integrative approach involving: i) protein-level measurement of multiple communication signals coupled to output responses in receiving cells; ii) mathematical modeling to uncover input-output relationships and interactions between signals. Using human dendritic cell (DC)-T helper (Th) cell communication as a model, we measured 36 DC-derived signals, and 17 Th cytokines broadly covering Th diversity, in 428 observations. We developed a data-driven computationally validated model capturing 56 already described, and 290 potentially novel mechanisms of Th cell specification. By predicting context-dependent behaviors, we demonstrated a new function for IL-12p70 as inducer of Th17 in an IL-1 signaling context. This work provides a unique resource to decipher the complex combinatorial rules governing DC-Th cell communication, and guide their manipulation for vaccine design and immunotherapies.

Keywords: Cell-cell communication, systems immunology, mathematical modeling, signal Integration, immunology, T helper cell differentiation, dendritic cells

Suggested Citation

Grandclaudon, Maximilien and Perrot-Dockès, Marie and Trichot, Coline and Mostafa-Abouzid, Omar and Abou-Jaoudé, Wassim and Berger, Frédérique and Hupé, Philippe and Thieffry, Denis and Sansonnet, Laure and Chiquet, Julien and Levy-Leduc, Céline and Soumelis, Vassili, A Quantitative Multivariate Model of Human Dendritic Cell-T Helper Cell Communication (March 15, 2019). Available at SSRN: https://ssrn.com/abstract=3353217 or http://dx.doi.org/10.2139/ssrn.3353217
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Maximilien Grandclaudon

PSL Research University - Centre de Recherche

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Marie Perrot-Dockès

University of Paris-Saclay - UMR MIA-Paris

55 Avenue de Paris
Versailles, 78000
France

Coline Trichot

PSL Research University - Centre de Recherche

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Omar Mostafa-Abouzid

PSL Research University - Centre de Recherche

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Wassim Abou-Jaoudé

École Normale Supérieure - PSL Research University - Computational Systems Biology Team

Paris
France

Frédérique Berger

PSL Research University - Centre de Recherche

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Philippe Hupé

PSL Research University - Centre de Recherche

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Denis Thieffry

École Normale Supérieure - PSL Research University - Computational Systems Biology Team

Paris
France

Laure Sansonnet

University of Paris-Saclay - UMR MIA-Paris

55 Avenue de Paris
Versailles, 78000
France

Julien Chiquet

University of Paris-Saclay - UMR MIA-Paris

55 Avenue de Paris
Versailles, 78000
France

Céline Levy-Leduc

University of Paris-Saclay - UMR MIA-Paris

55 Avenue de Paris
Versailles, 78000
France

Vassili Soumelis (Contact Author)

Université Paris VI Pierre et Marie Curie - Research Center ( email )

175 Rue du Chevaleret
Paris, 75013
France

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