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Updated: May 10, 2026
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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
A validated regulatory network for Th17 cell specification
Maria Ciofani1, Aviv Madar, Carolina Galan
1Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Cell
|October 2, 2012
Summary
Researchers mapped the regulatory network controlling T helper 17 (Th17) cell differentiation. This reveals key transcription factors like RORγt and BATF, offering new therapeutic targets for inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Systems Biology
Background:
- T helper 17 (Th17) cells are crucial for mucosal immunity but also implicated in inflammatory diseases.
- Th17 cell differentiation is orchestrated by a complex interplay of transcription factors (TFs), including RORγt.
Purpose of the Study:
- To delineate the global transcriptional regulatory network governing Th17 cell differentiation.
- To identify novel regulators and understand the hierarchical roles of key TFs.
Main Methods:
- Utilized an iterative systems biology approach combining genome-wide TF occupancy, TF mutant expression profiling, and time-series expression data.
- Integrated multiple datasets to build and validate a predictive model of the Th17 regulatory network.
Main Results:
- Identified BATF and IRF4 as critical for initial chromatin accessibility and transcriptional initiation.
- Demonstrated that RORγt plays a focal, deterministic role in globally tuning the Th17 transcriptional program.
- Discovered new Th17 regulators, including Fosl2, highlighting its role in cellular plasticity.
Conclusions:
- The study presents a comprehensive map of the Th17 transcriptional regulatory network.
- The validated predictive model offers insights into TF cooperation and hierarchical control.
- Identified regulators and network dynamics provide a foundation for developing novel therapeutic strategies for Th17-mediated inflammatory diseases.
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