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Upstream stimulating factors regulate the expression of RORγT in human lymphocytes
Marcin Ratajewski1, Aurelia Walczak-Drzewiecka, Anna Salkowska
1Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland.
Journal of Immunology (Baltimore, Md. : 1950)
|August 15, 2012
Summary
Transcription factors upstream stimulatory factor 1 (USF-1) and USF-2 are essential for regulating retinoic acid-related orphan receptor γT (RORγT) gene expression in human lymphocytes. Their upregulation during Th17 cell differentiation highlights their role in this crucial immune process.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Retinoic acid-related orphan receptor γT (RORγT) is a key nuclear receptor governing Th17 cell development and IL-17 expression.
- The transcriptional regulation of RORγT during human Th17 cell differentiation remains incompletely understood.
Purpose of the Study:
- To elucidate the transcriptional mechanisms controlling RORγT expression in human lymphocytes.
- To identify key transcription factors involved in RORγT gene regulation.
Main Methods:
- Analysis of the human RORγT promoter using 5' deletion and in situ mutagenesis.
- Chromatin immunoprecipitation assays.
- Overexpression studies of candidate transcription factors.
Main Results:
- Upstream stimulatory factor 1 (USF-1) and USF-2 were identified as indispensable transcription factors for RORγT transcription in human lymphocytes.
- Expression levels of USF-1 and USF-2 were found to increase during Th17 cell differentiation from naive CD4+ T cells.
- This study presents the first analysis of the human RORγT promoter and establishes the role of USFs in its regulation.
Conclusions:
- USF-1 and USF-2 are critical regulators of RORγT expression, playing a significant role in the molecular mechanisms of Th17 cell differentiation.
- Dysregulation of USF expression may be relevant to inflammatory conditions characterized by Th17 cell involvement.
- These findings suggest a potential link between metabolic disorders, USF expression, and autoimmune diseases associated with RORγT upregulation.
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