Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2017-04, Vol.46 (4), p.609-620

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Cytokine penetration in tissues is governed by a diffusion-consumption mechanism•Spherical cytokine niches are generated around cytokine-producing cells•The characteristic niche size depends on the density of cytokine consumers•Cytokine niches are a source of variability in otherwise identical cells Cytokine-mediated communication allows immune cells to achieve a context-appropriate response, but the distance over which this communication happens is unclear. Oyler-Yaniv et al. (2017) show that a simple diffusion-consumption mechanism quantitatively describes the spatial spread of cytokines in vivo and results in localized niches of high cytokine concentrations that contribute to cell-to-cell variability.