Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut

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Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut

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Title: Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut
Author: Schlenner, Susan M.; Weigmann, Benno; Ruan, Qingguo; Chen, Youhai; von Boehmer, Harald

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Citation: Schlenner, Susan M., Benno Weigmann, Qingguo Ruan, Youhai Chen, and Harald von Boehmer. 2012. Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory t cells with the exception of the gut. The Journal of Experimental Medicine 209(9): 1529-1535.
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Abstract: Regulatory T cells (T reg cells) are essential for the prevention of autoimmunity throughout life. T reg cell development occurs intrathymically but a subset of T reg cells can also differentiate from naive T cells in the periphery. In vitro, Smad signaling facilitates conversion of naive T cells into T reg cells but results in unstable Foxp3 expression. The TGF-β–Smad response element in the foxp3 locus is located in the CNS1 region in close proximity to binding sites for transcription factors implicated in TCR and retinoic acid signaling. From in vitro experiments it was previously postulated that foxp3 transcription represents a hierarchical process of transcription factor binding in which Smad3 would play a central role in transcription initiation. However, in vitro conditions generate T reg cells that differ from T reg cells encountered in vivo. To address the relevance of Smad3 binding to the CNS1 enhancer in vivo, we generated mice that exclusively lack the Smad binding site (foxp3CNS1mut). We show that binding of Smad3 to the foxp3 enhancer is dispensable for T reg cell development in newborn and adult mice with the exception of the gut.
Published Version: doi:10.1084/jem.20112646
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428940/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10594308
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