title: Design principles of cell circuits with paradoxical components.
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.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Hart
authors.forename: Yaron E
authors.initials: YE
authors.lastname: Antebi
authors.forename: Avraham E
authors.initials: AE
authors.lastname: Mayo
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D049109:Cell Proliferation; D015870:Gene Expression / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D009284:Naphthols; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014227:Triazines
chemical_list: C409762:2-(3-aminophenol)-6-(4-amino-1-naphthol)-4-chloro-triazine; C508594:IL2 protein, human; D007376:Interleukin-2; D007378:Interleukins; C464565:MYDGF protein, human; D009284:Naphthols; D016212:Transforming Growth Factor beta; D014227:Triazines