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Nat Immunol. 2017 Feb;18(2):173-183. doi: 10.1038/ni.3646. Epub 2016 Dec 19.

Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment.

Author information

1
Department of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
2
Laboratory of Experimental Immunology, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
3
Immuno-Genomics Research Unit, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
4
Laboratory of Integrative Biological Science, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
5
Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
6
Department of Molecular Immunology, School of Medicine, Toho University, Tokyo, Japan.
7
Laboratory for Transcriptional Regulation, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
8
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

Abstract

Most Foxp3+ regulatory T (Treg) cells develop in the thymus as a functionally mature T cell subpopulation specialized for immune suppression. Their cell fate appears to be determined before Foxp3 expression; yet molecular events that prime Foxp3- Treg precursor cells are largely obscure. We found that Treg cell-specific super-enhancers (Treg-SEs), which were associated with Foxp3 and other Treg cell signature genes, began to be activated in Treg precursor cells. T cell-specific deficiency of the genome organizer Satb1 impaired Treg-SE activation and the subsequent expression of Treg signature genes, causing severe autoimmunity due to Treg cell deficiency. These results suggest that Satb1-dependent Treg-SE activation is crucial for Treg cell lineage specification in the thymus and that its perturbation is causative of autoimmune and other immunological diseases.

PMID:
27992401
PMCID:
PMC5582804
DOI:
10.1038/ni.3646
[Indexed for MEDLINE]
Free PMC Article

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