RT Journal Article
SR Electronic
T1 Spatio-temporal modeling reveals a layer of tunable control circuits for the distribution of cytokines in tissues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.17.484722
DO 10.1101/2022.03.17.484722
A1 Patrick Brunner
A1 Lukas Kiwitz
A1 Kevin Thurley
YR 2022
UL http://biorxiv.org/content/early/2022/04/04/2022.03.17.484722.abstract
AB Cytokines are diffusible mediators of cell-cell communication among immune cells with critical regulatory functions for cell differentiation and proliferation. Previous studies have revealed considerable spatial inhomogeneities in the distribution of cytokine molecules in tissues, potentially shaping the efficacy and range of paracrine cytokine signals. How such cytokine gradients emerge and are controlled within cell populations is incompletely understood. In this work, we employed a spatial reaction-diffusion model to systematically investigate the formation and influence of spatial cytokine gradients. We found the fraction of cytokine secreting cells to be the main source of spatial inhomogeneity and subsequent activation. Positive feedback from local cytokine levels upon cytokine receptor expression leads to further increased spatial cytokine inhomogeneities. By exploring the effect of co-clustering cytokine secreting cells and cells with large amounts of receptor expression, as in the presence of regulatory T cells in the vicinity of antigen-presenting cells, we found that such constrained tissue architecture can have profound effects on the range of paracrine cytokine signals.Competing Interest StatementThe authors have declared no competing interest.