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