Computational modeling uncovers new molecular mechanisms controlling T helper cell function

BLACKSBURG, Va., April 04, 2013 – Researchers at the Center for Modeling Immunity to Enteric Pathogens (MIEP) at Virginia Bioinformatics Institute (VBI) believe they have identified the mechanism that turns pro-inflammatory Th17 cells into anti-inflammatory T regulatory cells in the gut. This marks the first time that a comprehensive computational and mathematical model of the mechanisms governing Th cell differentiation has been created and key model-derived predictions have been validated experimentally. The results are published in PLOS Computational Biology.

The study focuses on PPAR γ, a protein that aids in metabolic regulation. In previous work, researchers at VBI’s Nutritional Immunology and Molecular Medicine Laboratory (NIMML) demonstrated that PPAR γ plays a crucial role in suppressing inflammation and immune responses. The new model developed by the MIEP team predicted a novel role of PPAR γ in controlling how gut-associated Th cells change from pro-inflammatory to anti-inflammatory types.

“Th cells play important roles in orchestrating immune responses, and their functions are controlled by complex signaling pathways with abundant feedback loops. In this project, we used computational and mathematical modeling to more comprehensively characterize the mechanisms controlling Th cell differentiation and plasticity at the systems level. We provide evidence demonstrating that PPAR γ activation controls the switch from pathogenic Th17 cells into regulatory T cells in the gut,” said Josep Bassaganya-Riera, professor of immunology, director of NIMML, and principal investigator of MIEP.

According to the researchers, the precision with which computational models unravel complex biological networks brings researchers closer to understanding how immune responses are shaped by genetics, environmental cues and disease states. The systems immunology approaches developed by MIEP may help researchers and clinicians identify targets that will yield more effective therapies for infectious and immune-mediated diseases.

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MIEP is funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under Contract No. HHSN272201000056C. PI: Josep Bassaganya-Riera.

About the Nutritional Immunology and Molecular Medicine Laboratory: The Nutritional Immunology and Molecular Medicine Laboratory (NIMML) conducts translational research aimed at developing novel therapeutic and prophylactic approaches for modulating immune and inflammatory responses. The Laboratory has over 20 researchers and combines computational modeling, bioinformatics approaches, pre-clinical experimentation and human clinical studies to better understand the mechanisms of immune regulation at mucosal surfaces and ultimately accelerate the development of novel treatments for infectious and immune-mediated diseases. In addition, the NIMML team leads the NIAID-funded Center for Modeling Immunity to Enteric Pathogens .

About the Virginia Bioinformatics Institute The Virginia Bioinformatics Institute at Virginia Tech is a premier bioinformatics, computational biology and systems biology research facility that uses transdisciplinary approaches to science, combining information technology, biology and medicine. These approaches are used to interpret and apply vast amounts of biological data generated from basic research to some of today’s key challenges in the biomedical, environmental and agricultural sciences. With more than 240 highly trained multidisciplinary, international personnel, research at the institute involves collaboration in diverse disciplines such as mathematics, computer science, biology, plant pathology, biochemistry, systems biology, computational immunology, statistics, economics, synthetic biology and medicine. The large amounts of data generated by this approach are analyzed and interpreted to create new knowledge that is disseminated to the world’s scientific, governmental and wider communities.

Tiffany Trent