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Genome-wide identification of human FOXP3 target genes in natural regulatory T cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Melville, Elizabeth L. Pederson, Stephen Shannon, M. Frances Goodall, Gregory J. D'Andrea, Richard J. Bresatz, Suzanne Glonek, Gary G. Gargett, Tessa Barry, Simon C. Peng, Kaimen Sadlon, Timothy J. Brown, Cheryl Y. Zola, Heddy Wilkinson, Bridget G.
Description	Country affiliation: Australia Author Affiliation: Sadlon TJ ( Molecular Immunology Laboratory, Women's and Children's Health Research Institute, Women's and Children's Hospital, North Adelaide, South Australia, Australia.)
Abstract	The transcription factor FOXP3 is essential for the formation and function of regulatory T cells (Tregs), and Tregs are essential for maintaining immune homeostasis and tolerance. This is demonstrated by a lethal autoimmune defect in mice lacking Foxp3 and in immunodysregulation polyendocrinopathy enteropathy X-linked syndrome patients. However, little is known about the molecular basis of human FOXP3 function or the relationship between direct and indirect targets of FOXP3 in human Tregs. To investigate this, we have performed a comprehensive genome-wide analysis for human FOXP3 target genes from cord blood Tregs using chromatin immunoprecipitation array profiling and expression profiling. We have identified 5579 human FOXP3 target genes and derived a core Treg gene signature conserved across species using mouse chromatin immunoprecipitation data sets. A total of 739 of the 5579 FOXP3 target genes were differentially regulated in Tregs compared with Th cells, thus allowing the identification of a number of pathways and biological functions overrepresented in Tregs. We have identified gene families including cell surface molecules and microRNAs that are differentially expressed in FOXP3(+) Tregs. In particular, we have identified a novel role for peptidase inhibitor 16, which is expressed on the cell surface of >80% of resting human CD25(+)FOXP3(+) Tregs, suggesting that in conjunction with CD25 peptidase inhibitor 16 may be a surrogate surface marker for Tregs with potential clinical application.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	2
Volume Number	185
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2010-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Forkhead Transcription Factors Immunology Gene Expression Profiling Gene Expression Regulation Genome, Human Genetics T-lymphocytes, Regulatory Metabolism Animals Binding Sites Cell Proliferation Cell Separation Cells, Cultured Chromatin Immunoprecipitation Fetal Blood Cytology Flow Cytometry Mice Promoter Regions, Genetic Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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