Design principles of cell circuits with paradoxical components

Yuval Hart, Yaron E. Antebi, Avraham E. Mayo, Nir Friedman, Uri Alona*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Biological systems display complex networks of interactions both at the level of molecules inside the cell and at the level of interactions between cells. Networks of interacting molecules, such as transcription networks, have been shown to be composed of recurring circuits called network motifs, each with specific dynamical functions. Much less is known about the possibility of such circuit analysis in networks made of communicating cells. Here, we study models of circuits in which a few cell types interact by means of signaling molecules. We consider circuits of cells with architectures that seem to recur in immunology. An intriguing feature of these circuits is their use of signaling molecules with a pleiotropic or paradoxical role, such as cytokines that increase both cell growth and cell death. We find that pleiotropic signaling molecules can provide cell circuits with systems-level functions. These functions include for different circuits maintenance of homeostatic cell concentrations, robust regulation of differentiation processes, and robust pulses of cells or cytokines.

Original languageAmerican English
Pages (from-to)8346-8351
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number21
DOIs
StatePublished - 22 May 2012
Externally publishedYes

Keywords

  • IL-2
  • IL-27
  • T helper cells
  • TGF-β
  • Tregs

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