Article abstract
Nature Immunology 9, 1297 - 1306 (2008)
Published online: 12 October 2008 | Corrected online: 14 November 2008 | doi:10.1038/ni.1663
There is a Corrigendum (February 2009) associated with this Article.
Interactions among the transcription factors Runx1, ROR
t and Foxp3 regulate the differentiation of interleukin 17–producing T cells
Fuping Zhang1, Guangxun Meng1 & Warren Strober1
Abstract
The molecular mechanisms underlying the differentiation of interleukin 17–producing T helper cells (TH-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors ROR
t and Runx1. Runx1 influenced TH-17 differentiation by inducing RORt expression and by binding to and acting together with RORt during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on TH-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with RORt regulates TH-17 differentiation.
- Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Correspondence to: Warren Strober1 e-mail: wstrober@niaid.nih.gov
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