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

  • Cell. 2019 Oct 3;179(2):432-447.e21. doi: 10.1016/j.cell.2019.09.012.
Maximilien Grandclaudon  1 ,  Marie Perrot-Dockès  2 ,  Coline Trichot  1 ,  Léa Karpf  1 ,  Omar Abouzid  1 ,  Camille Chauvin  1 ,  Philémon Sirven  1 ,  Wassim Abou-Jaoudé  3 ,  Frédérique Berger  4 ,  Philippe Hupé  5 ,  Denis Thieffry  3 ,  Laure Sansonnet  2 ,  Julien Chiquet  2 ,  Céline Lévy-Leduc  2 ,  Vassili Soumelis  6
Affiliations
  • 1. Institut Curie, Centre de Recherche, PSL Research University, 75005 Paris, France; INSERM U932, Immunity and Cancer, 75005 Paris, France.
  • 2. UMR MIA-Paris, AgroParisTech, INRA-Université Paris-Saclay, 75005 Paris, France.
  • 3. Computational Systems Biology Team, Institut de Biologie de l'École Normale Supérieure, Centre National de la Recherche Scientifique UMR8197, INSERM U1024, École Normale Supérieure, PSL Université, 75005 Paris, France.
  • 4. Institut Curie, Centre de Recherche, PSL Research University, 75005 Paris, France; Institut Curie, PSL Research University, Unit of Biostatistics, 75005 Paris, France; Institut Curie, PSL Research University, INSERM U900, 75005 Paris, France.
  • 5. Institut Curie, Centre de Recherche, PSL Research University, 75005 Paris, France; Institut Curie, PSL Research University, INSERM U900, 75005 Paris, France; Mines Paris Tech, 77305 Cedex Fontainebleau, France.
  • 6. Institut Curie, Centre de Recherche, PSL Research University, 75005 Paris, France; INSERM U932, Immunity and Cancer, 75005 Paris, France. Electronic address: [email protected].
PMID: 31585082 DOI: 10.1016/j.cell.2019.09.012
Abstract

Cell-cell communication involves a large number of molecular signals that function as words of a complex language whose grammar remains mostly unknown. Here, we describe an integrative approach involving (1) protein-level measurement of multiple communication signals coupled to output responses in receiving cells and (2) 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 demonstrate a new function for IL-12p70 as an 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
T helper cell differentiation; cell-cell communication; dendritic cells; immunology; mathematical modeling; signal integration; systems immunology.