ArticlePLoS computational biology2013
Systems modeling of molecular mechanisms controlling cytokine-driven CD4+ T cell differentiation and phenotype plasticity.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
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- Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data.NPJ systems biology and applications · 2024Article
- PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cells.Life science alliance · 2023Article
- CD4+ T Cell Regulatory Network Underlies the Decrease in Th1 and the Increase in Anergic and Th17 Subsets in Severe COVID-19.Pathogens (Basel, Switzerland) · 2022Article
- Computational modeling of complex bioenergetic mechanisms that modulate CD4+ T cell effector and regulatory functions.NPJ systems biology and applications · 2022Article
- Interferon-β acts directly on T cells to prolong allograft survival by enhancing regulatory T cell induction through Foxp3 acetylation.Immunity · 2022Article
- Targeting ProteinCells · 2022Review
- An integrative systems biology view of host-pathogen interactions: The regulation of immunity and homeostasis is concomitant, flexible, and smart.Frontiers in immunology · 2022Article
- Beyond the Finish Line: The Impact and Dynamics of Biomarkers in Physical Exercise-A Narrative Review.Journal of clinical medicine · 2021Review
- Integrative computational approach identifies drug targets in CD4NPJ systems biology and applications · 2021Article
- Exercise-induced downregulation of serum interleukin-6 and tumor necrosis factor-alpha in Egyptian handball players.Saudi journal of biological sciences · 2021Article
- Continuous Modeling of T CD4 Lymphocyte Activation and Function.Frontiers in immunology · 2021Article
- Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy.Frontiers in cell and developmental biology · 2021Review
- The role of GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals in Th17 responses counteracted by PPARγ agonists.Theranostics · 2021Article
- A Dynamic Quantitative Systems Pharmacology Model of Inflammatory Bowel Disease: Part 1 - Model Framework.Clinical and translational science · 2021Article
- Circulating immune cell phenotype dynamics reflect the strength of tumor-immune cell interactions in patients during immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Interplay between Cytokine Circuitry and Transcriptional Regulation Shaping Helper T Cell Pathogenicity and Plasticity in Inflammatory Bowel Disease.International journal of molecular sciences · 2020Review
- A case for the reuse and adaptation of mechanistic computational models to study transplant immunology.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Review
- Goals in Nutrition Science 2020-2025.Frontiers in nutrition · 2020Review
- Th17 Cells in Helicobacter pylori Infection: a Dichotomy of Help and Harm.Infection and immunity · 2019Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARγ) in modulating plasticity between Th17 and iTreg cells. PPARγ regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARγ activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPARγ. Deletion of PPARγ in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARγ in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.