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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Communication / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Healthy Volunteers
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-12 / physiology*
  • Middle Aged
  • Models, Biological
  • Th17 Cells / immunology*
  • Young Adult


  • Interleukin-1
  • Interleukin-12