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PMID: 19185518 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells.

Immunity ·Vol. 30 ·No. 2 ·2009-02-20 ·Pages 204-17

Yu A, Zhu L, Altman NH, Malek TR

Abstract

Interleukin-2 receptor (IL-2R) signaling is essential for T regulatory (Treg) cell development and homeostasis. Here, we show that expression of IL-2Rbeta chains that lack tyrosine residues important for the association of the adaptor Shc and the transcription factor STAT5 in IL-2Rbeta-deficient mice resulted in production of a normal proportion of natural Treg cells that suppressed severe autoimmunity related with deficiency in IL-2 or IL-2R. These mutant IL-2Rbeta chains supported suboptimal and transient STAT5 activation that upregulate the transcription factor Foxp3 to normal amounts in natural, but not induced, Treg cells. Nevertheless, gene expression profiling revealed many targets in peripheral natural Treg cells that were IL-2 dependent and a substantial overlap between the Treg cell IL-2-dependent gene program and the Treg cell transcriptional signature. Collectively, these findings demonstrate that a critical, and perhaps minor, subset of IL-2-dependent targets is indexed to a low IL-2R signaling threshold and that a substantial proportion of the Treg cell gene program is regulated by IL-2.

MeSH Terms
Animals Autoimmunity/immunology Cell Proliferation Cells, Cultured Forkhead Transcription Factors/immunology Gene Expression Profiling Homeostasis/immunology Immunity, Innate/immunology Interleukin-2 Receptor beta Subunit/deficiency,genetics,immunology,metabolism Lymphocyte Count Mice Mice, Inbred C57BL Mice, Knockout Mutation/genetics Signal Transduction/immunology T-Lymphocytes, Regulatory/cytology,immunology
Chemicals
Forkhead Transcription Factors Foxp3 protein, mouse Interleukin-2 Receptor beta Subunit
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yu Aixin
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Zhu Linjian
Altman Norman H
Malek Thomas R
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.11.014
Published
2009-02-20
Epub
2009-00-29
Pages
204-17
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2962446
Subset
IM
Grants
NIAID NIH HHS · R01 AI055815 · United States
NCI NIH HHS · R01 CA045957 · United States
NCI NIH HHS · R01 CA045957-23 · United States
NCI NIH HHS · CA45957 · United States
NCI NIH HHS · P01 CA109094-040001 · United States
NCI NIH HHS · CA109094 · United States
NIAID NIH HHS · R01 AI055815-05 · United States
NIAID NIH HHS · AI040114 · United States
NCI NIH HHS · P01 CA109094 · United States
Databases
GEO
GSE14350
External Links
PubMed source DOI: 10.1016/j.immuni.2008.11.014 PMC Full Text View journal details
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