Article
- The EMBO Journal (2007) 26, 1292 - 1302
- doi:10.1038/sj.emboj.7601586
Published online: 15 February 2007
Subject Categories:
Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12R
2 expression during human Th1 cell differentiation
Fabrice A Letimier1,a, Nadia Passini2,a, Sona Gasparian1, Elisabetta Bianchi1 and Lars Rogge1
- Immunoregulation Laboratory, Department of Immunology, Institut Pasteur, Paris, France
- Bioxell SpA, Milano, Italy
Correspondence to:
Lars Rogge, Immunoregulation Laboratory, Department of Immunology, Institut Pasteur, 25 rue du Dr Roux, Paris 75724, France. Tel.: +33 1 4061 3822; Fax: +33 1 4061 3204; E-mail: lrogge@pasteur.fr
aThese authors contributed equally to this work
Received 12 July 2006; Accepted 11 January 2007
Abstract
Interleukin-12 (IL-12) is a key cytokine for the development of T helper type 1 (Th1) responses; however, naïve CD4+ T cells do not express IL-12R
2, and are therefore unresponsive to IL-12. We have examined the mechanisms that control Th1-specific expression of the human IL-12R2 gene at early time points after T-cell stimulation. We have identified a Th1-specific enhancer element that binds signal transducer and activator of transcription 4 (STAT4) in vivo in developing Th1 but not Th2 cells. T-cell receptor (TCR) signaling induced histone hyperacetylation and recruitment of BRG1, the ATPase subunit of the SWI/SNF-like BAF chromatin remodeling complex, to the IL-12R2 regulatory regions and was associated with low-level gene transcription at the IL-12R2 locus. However, high-level IL-12R2 expression required TCR triggering in the presence of IL-12. Our results indicate a synergistic role of TCR-induced chromatin remodeling and cytokine-induced STAT4 activation to direct IL-12R2 expression during Th1 cell development.
Keywords:
- BRG1,
- chromatin remodeling,
- interleukin-12,
- STAT4,
- Th1 cell differentiation
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