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

Maximilien Grandclaudon (1, 2) , Marie Perrot-Dockes (3) , Coline Trichot (1, 2) , Léa Karpf (1, 2) , Omar Abouzid (1, 2) , Camille Chauvin (1, 2) , Philemon Sirven (1, 2) , Wassim Abou-Jaoudé (4) , Frederique Berger (5, 6, 2) , Philippe Hupé (6, 7, 2) , Denis Thieffry (4) , Laure Sansonnet (3) , Julien Chiquet (3) , Céline Lévy-Leduc (3) , Vassili Soumelis (2)

1 U932 - Immunité et cancer
2 Institut Curie [Paris]
3 MIA-Paris - Mathématiques et Informatique Appliquées
4 IBENS - Institut de biologie de l'ENS Paris
5 INSERM - Institut National de la Santé et de la Recherche Médicale
6 PSL - Université Paris sciences et lettres
7 Mines Paris - PSL (École nationale supérieure des mines de Paris)

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: health; lineage; selection; plasticity; stimulation; differentitation; regulatory network; growth-factor-beta

Domains: Life Sciences [q-bio]

Maximilien Grandclaudon, Marie Perrot-Dockes, Coline Trichot, Léa Karpf, Omar Abouzid, et al.. A Quantitative Multivariate Model of Human Dendritic Cell-T Helper Cell Communication. Cell, 2019, 179 (2), pp.432-447.e21. ⟨10.1016/j.cell.2019.09.012⟩. ⟨hal-02316607⟩