Foxp3 Controls Regulatory T-cell Function by Interacting with Aml1/Runx1.
From: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Nature
- Publish Date: Apr 2007
- ISSN: 1476-4687
- Volume: 446
- Issue: 7136
- Pages: 685-9
- Medium: Internet
- Language: English
- Citation (JAMA): Ono Masahiro, Yaguchi Hiroko, Ohkura Naganari, et al. Foxp3 Controls Regulatory T-cell Function by Interacting with Aml1/Runx1.. Nature Apr 2007;446:685-9
Abstract
Naturally arising CD25+CD4+ regulatory T cells (T(R) cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy. T(R) cells specifically express the transcription factor Foxp3, a key regulator of T(R)-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and upregulate T(R)-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development, activates IL-2 and IFN-gamma gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural T(R) cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN-gamma production, upregulates T(R)-cell-associated molecules, and exerts suppressive activity. This transcriptional control of T(R)-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.
Mesh Headings (Keywords): Animals, Core Binding Factor Alpha 2 Subunit, Forkhead Transcription Factors, Gene Expression Regulation, Humans, Interleukin-2, Lymphocyte Activation, Mice, Phenotype, Promoter Regions (Genetics), Protein Binding, T-Lymphocytes, Regulatory
Check for Full Text / PubMed Unique Identifier (PMID): 17377532
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