A Low Interleukin-2 Receptor Signaling Threshold Supports the Development and Homeostasis of T Regulatory Cells

Aixin Yu, Linjian Zhu, Norman H. Altman, Thomas Malek

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Interleukin-2 receptor (IL-2R) signaling is essential for T regulatory (Treg) cell development and homeostasis. Here, we show that expression of IL-2Rβ chains that lack tyrosine residues important for the association of the adaptor Shc and the transcription factor STAT5 in IL-2Rβ-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-2Rβ 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.

Original languageEnglish
Pages (from-to)204-217
Number of pages14
JournalImmunity
Volume30
Issue number2
DOIs
StatePublished - Feb 20 2009

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Interleukin-2 Receptors
Regulatory T-Lymphocytes
Homeostasis
Interleukin-2
STAT5 Transcription Factor
Gene Expression Profiling
Regulator Genes
Autoimmunity
Tyrosine
Transcription Factors
Up-Regulation
Genes

Keywords

  • CELLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

A Low Interleukin-2 Receptor Signaling Threshold Supports the Development and Homeostasis of T Regulatory Cells. / Yu, Aixin; Zhu, Linjian; Altman, Norman H.; Malek, Thomas.

In: Immunity, Vol. 30, No. 2, 20.02.2009, p. 204-217.

Research output: Contribution to journalArticle

Yu, Aixin ; Zhu, Linjian ; Altman, Norman H. ; Malek, Thomas. / A Low Interleukin-2 Receptor Signaling Threshold Supports the Development and Homeostasis of T Regulatory Cells. In: Immunity. 2009 ; Vol. 30, No. 2. pp. 204-217.
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