Puniya2021 - CD4+ Th1 cell metabolic model

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CD4+ T cells are critical components in the human immune system. They produce cytokines to fight against pathogens and abnormal cells and stimulate other cells, such as B cells, macrophages, and neutrophils, to generate an immune response. T helper 1 (Th1) cells are subtypes of CD4+ T cells that differentiate from naive CD4+ T cells in a specific cytokine environment. The Th1 cell model consists of 3956 reactions, 2517 metabolites, and 1133 genes. CD4+ T cell models helped identify drug targets and repurposable drugs against autoimmune diseases.
Related Publication
  • Integrative computational approach identifies drug targets in CD4+ T-cell-mediated immune disorders
  • Bhanwar Lal Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar
  • NPJ Systems Biology and Applications , 1/ 2021 , DOI: 10.1038/s41540-020-00165-3
  • Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, USA. Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. Centre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, UK. Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
  • CD4+ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immune-related diseases. CD4+ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4+ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico simulations for drug response analysis of existing FDA-approved drugs and compounds. Integration of disease-specific differentially expressed genes with altered reactions in response to metabolic perturbations identified 68 drug targets for the three autoimmune diseases. In vitro experimental validation, together with literature-based evidence, showed that modulation of fifty percent of identified drug targets suppressed CD4+ T cells, further increasing their potential impact as therapeutic interventions. Our approach can be generalized in the context of other diseases, and the metabolic models can be further used to dissect CD4+ T-cell metabolism.
Submitter of the first revision: Bhanwar Lal Puniya
Submitter of this revision: Bhanwar Lal Puniya
Modellers: Bhanwar Lal Puniya

Metadata information

Mathematical Modelling Ontology Constraint-based model

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Model files

T1M1133.xml SBML L3V1 representation of human CD4+ Th1 cell metabolism model. 6.86 MB Preview | Download

Additional files

FROG_T1M1133.zip FROG report of T1M1133 model 48.29 KB Preview | Download
T1M1133.fbc2.xml FBC v2 representation of T1M1133 model 7.01 MB Preview | Download
miniFROG_T1M1133_Th1.xlsx miniFROG report of T1M1133 model 29.84 KB Preview | Download

  • Model originally submitted by : Bhanwar Lal Puniya
  • Submitted: Jan 23, 2021 8:38:56 PM
  • Last Modified: Jun 11, 2022 12:32:20 AM
  • Version: 5 public model Download this version
    • Submitted on: Jun 11, 2022 12:32:20 AM
    • Submitted by: Bhanwar Lal Puniya
    • With comment: Added FROG and miniFROG reports.
  • Version: 4 public model Download this version
    • Submitted on: Jan 23, 2021 8:38:56 PM
    • Submitted by: Bhanwar Lal Puniya
    • With comment: Edited model metadata online.

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