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

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.
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https://hal-agroparistech.archives-ouvertes.fr/hal-02316607
Contributor : Céline Lévy-Leduc <>
Submitted on : Tuesday, October 15, 2019 - 2:18:19 PM
Last modification on : Saturday, September 19, 2020 - 4:48:28 AM

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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, Elsevier, 2019, 179 (2), pp.432-447.e21. ⟨10.1016/j.cell.2019.09.012⟩. ⟨hal-02316607⟩

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