Work

Inferring relevant control mechanisms for interleukin‐12 signaling in naïve CD4+T cells

Year: 2010

Type: article

Abstract: Interleukin-12 (IL-12) is a key cytokine involved in shaping the cell-mediated immunity to intracellular pathogens. IL-12 initiates a cellular response through the IL-12 signaling pathway, a member of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) family of signaling networks. The JAK/STAT pathway includes several regulatory elements; however, the dynamics of these mechanisms are not fully understood. Therefore, the objective of this study was to infer the relative importance of regulatory mechanisms that modulate the activation of STAT4 in naïve CD4(+) T cells. Dynamic changes in protein expression and activity were measured using flow cytometry and these data were used to calibrate a mathematical model of IL-12 signaling. An empirical Bayesian approach was used to infer the relative strengths of the different regulatory mechanisms in the system. The model predicted that IL-12 receptor expression is regulated by a dynamic, autonomous program that was independent of STAT4 activation. In summary, a mathematical model of the canonical IL-12 signaling pathway used in conjunction with a Bayesian framework provided high-confidence predictions of the system-specific control mechanisms from the available experimental observations.

Source: Immunology and Cell Biology

DOI: 10.1038/icb.2010.69

Authors: Stacey D Finley, Deepti Gupta, Ning Cheng, David J Klinke

Institutions: Northwestern University, West Virginia University

Language: English

Topic: Cytokine Signaling Pathways and Interactions

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Pharmaceutical Research and Manufacturers of America Foundation, National Cancer Institute, National Institute of Allergy and Infectious Diseases