Implementation of a regulatory gene network to simulate the TH1/2 differentiation in an agent-based model of hypersensitivity reactions

Authored by Filippo Castiglione, Daniele Santoni, Marco Pedicini

Date Published: 2008-06-01

DOI: 10.1093/bioinformatics/btn135

Sponsors: European Union

Platforms: No platforms listed

Model Documentation: Other Narrative Flow charts

Model Code URLs: Model code not found

Abstract

Motivation: An unbalanced differentiation of T helper cells from precursor type TH0 to the TH1 or TH2 phenotype in immune responses often leads to a pathological condition. In general, immune reactions biased toward TH1 responses may result in auto-immune diseases, while enhanced TH2 responses may cause allergic reactions. The aim of this work is to integrate a gene network of the TH differentiation in an agent-based model of the hyper-sensitivity reaction. The implementation of such a system introduces a second level of description beyond the mesoscopic level of the inter-cellular interaction of the agent-based model. The intra-cellular level consists in the cell internal dynamics of gene activation and transcription. The gene regulatory network includes genes-related molecules that have been found to be involved in the differentiation process in TH cells. Results: The simulator reproduces the hallmarks of an IgE-mediated hypersensitive reaction and provides an example of how to combine the mesoscopic level description of immune cells with the microscopic gene-level dynamics.

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