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

Tunable cell-to-cell communications in the immune system

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 m m, 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


Published Date: 
April, 2017