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Spatio-temporal modeling reveals a layer of tunable control circuits for the distribution of cytokines in tissues

Patrick Brunner, Lukas Kiwitz, View ORCID ProfileKevin Thurley
doi: https://doi.org/10.1101/2022.03.17.484722
Patrick Brunner
1Systems Biology of Inflammation, German Rheumatism Research Center Berlin, Germany
2Institute for Theoretical Biology, Humboldt University Berlin, Germany
3Institute for Experimental Oncology, Biomathematics Division, University Hospital Bonn, Germany
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Lukas Kiwitz
1Systems Biology of Inflammation, German Rheumatism Research Center Berlin, Germany
2Institute for Theoretical Biology, Humboldt University Berlin, Germany
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Kevin Thurley
1Systems Biology of Inflammation, German Rheumatism Research Center Berlin, Germany
2Institute for Theoretical Biology, Humboldt University Berlin, Germany
3Institute for Experimental Oncology, Biomathematics Division, University Hospital Bonn, Germany
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  • ORCID record for Kevin Thurley
  • For correspondence: kevin.thurley@uni-bonn.de
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Abstract

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 Statement

The authors have declared no competing interest.

Footnotes

  • Small correction in Figure 2.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 04, 2022.
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Spatio-temporal modeling reveals a layer of tunable control circuits for the distribution of cytokines in tissues
Patrick Brunner, Lukas Kiwitz, Kevin Thurley
bioRxiv 2022.03.17.484722; doi: https://doi.org/10.1101/2022.03.17.484722
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Spatio-temporal modeling reveals a layer of tunable control circuits for the distribution of cytokines in tissues
Patrick Brunner, Lukas Kiwitz, Kevin Thurley
bioRxiv 2022.03.17.484722; doi: https://doi.org/10.1101/2022.03.17.484722

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