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

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Grandclaudon, Maximilien | Perrot-Dockes, Marie | Trichot, Coline | Karpf, Léa | Abouzid, Omar | Chauvin, Camille | Sirven, Philemon | Abou-Jaoudé, Wassim | Berger, Frederique | Hupé, Philippe | Thieffry, Denis | Sansonnet, Laure | Chiquet, Julien | Lévy-Leduc, Céline | Soumelis, Vassili

Edité par CCSD ; Elsevier -

International audience. 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.

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