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|Title:||Genome-wide identification of human FOXP3 target genes in natural regulatory T cells|
|Citation:||Journal of Immunology, 2010; 185(2):1071-1081|
|Publisher:||Amer Assoc Immunologists|
|Timothy J. Sadlon, Bridget G. Wilkinson, Stephen Pederson, Cheryl Y. Brown, Suzanne Bresatz, Tessa Gargett, Elizabeth L. Melville, Kaimen Peng, Richard J. D’Andrea, Gary G. Glonek, Gregory J. Goodall, Heddy Zola, M. Frances Shannon and Simon C. Barry|
|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.|
|Keywords:||Cells, Cultured; Fetal Blood; Animals; Humans; Mice; Flow Cytometry; Cell Separation; Chromatin Immunoprecipitation; Gene Expression Profiling; Cell Proliferation; Gene Expression Regulation; Binding Sites; Base Sequence; Genome, Human; T-Lymphocytes, Regulatory; Forkhead Transcription Factors; Promoter Regions, Genetic|
|Rights:||Copyright © 2010 by The American Association of Immunologists, Inc.|
|Appears in Collections:||Paediatrics publications|
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