A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System

Alon Oyler-Yaniv, Jennifer Oyler-Yaniv, Benjamin M. Whitlock, Zhiduo Liu, Ronald N. Germain, Morgan Huse, Grégoire Altan-Bonnet, Oleg Krichevsky

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Immune cells communicate by exchanging cytokines to achieve a context-appropriate response, but the distances over which such communication happens are not known. Here, we used theoretical considerations and experimental models of immune responses in vitro and in vivo to quantify the spatial extent of cytokine communications in dense tissues. We established that competition between cytokine diffusion and consumption generated spatial niches of high cytokine concentrations with sharp boundaries. The size of these self-assembled niches scaled with the density of cytokine-consuming cells, a parameter that gets tuned during immune responses. In vivo, we measured interactions on length scales of 80–120 μm, which resulted in a high degree of cell-to-cell variance in cytokine exposure. Such heterogeneous distributions of cytokines were a source of non-genetic cell-to-cell variability that is often overlooked in single-cell studies. Our findings thus provide a basis for understanding variability in the patterning of immune responses by diffusible factors.

Original languageEnglish
Pages (from-to)609-620
Number of pages12
JournalImmunity
Volume46
Issue number4
DOIs
StatePublished - 18 Apr 2017

Keywords

  • Cell-to-cell communications
  • Cell-to-cell variability
  • Cytokine niches
  • Cytokines
  • Diffusion/Consumption
  • Interleukin-2
  • Quantitative Immunology
  • STAT5
  • Theoretical Modeling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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