title: Demystifying the cytokine network: Mathematical models point the way.
abstract: Cytokines provide the means by which immune cells communicate with each other and with parenchymal cells. There are over one hundred cytokines and many exist in families that share receptor components and signal transduction pathways, creating complex networks. Reductionist approaches to understanding the role of specific cytokines, through the use of gene-targeted mice, have revealed further complexity in the form of redundancy and pleiotropy in cytokine function. Creating an understanding of the complex interactions between cytokines and their target cells is challenging experimentally. Mathematical and computational modeling provides a robust set of tools by which complex interactions between cytokines can be studied and analyzed, in the process creating novel insights that can be further tested experimentally. This review will discuss and provide examples of the different modeling approaches that have been used to increase our understanding of cytokine networks. This includes discussion of knowledge-based and data-driven modeling approaches and the recent advance in single-cell analysis. The use of modeling to optimize cytokine-based therapies will also be discussed.
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, USA. Electronic address: morel@pitt.edu.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Morel
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Robin E C
authors.initials: REC
authors.lastname: Lee
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Faeder
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological
chemical_list: D016207:Cytokines
keywords: CD4 T cell differentiation; Cytokine networks; Mathematical modeling; Single-cell analysis