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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation
Xinshou Ouyang1, Ruihua Zhang, Jianjun Yang
1Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York 10029, USA.
Nature Communications
|May 19, 2011
Summary
Interferon regulatory factor 8 (IRF8) acts as a brake on T helper 17 (T(H)17) cell development. IRF8 deficiency enhances T(H)17 cell differentiation, worsening inflammatory diseases like colitis.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- T helper 17 (T(H)17) cells are crucial in autoimmune diseases and inflammation.
- RORγt is essential for T(H)17 cell generation, but regulatory mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of Interferon Regulatory Factor 8 (IRF8) in T(H)17 cell differentiation.
- To elucidate the molecular mechanisms by which IRF8 influences T(H)17 cell function.
Main Methods:
- Utilized knockout mouse models with conventional and T cell-specific deletion of the Irf8 gene.
- Examined T(H)17 cell populations and inflammatory responses in an experimental colitis model.
- Investigated the physical interaction between IRF8 and RORγt.
Main Results:
- Mice lacking Irf8 showed increased T(H)17 cell generation.
- IRF8 deficiency led to exacerbated inflammation and a pronounced T(H)17 phenotype in a colitis model.
- IRF8 expression increased during T(H)17 lineage commitment, inhibiting differentiation.
Conclusions:
- IRF8 acts as a novel intrinsic transcriptional inhibitor of T(H)17 cell differentiation.
- IRF8 directly interacts with RORγt to regulate T(H)17 cell development.
- Targeting IRF8 may offer therapeutic strategies for T(H)17-mediated inflammatory conditions.
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