STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+ CD25- effector T cells

Laura Passerini, Sarah E. Allan, Manuela Battaglia, Sara Di Nunzio, Alicia N. Alstad, Megan K. Levings, Maria G. Roncarolo, Rosa Bacchetta

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Forkhead box P3 (FOXP3) is considered a specific marker for CD4+CD25+ regulatory T (Treg) cells, but increasing evidence suggests that human CD4+CD25- effector T (Teff) cells can transiently express FOXP3 upon activation. We demonstrate that the signal transducer and activator of transcription 5 (STAT5)-signaling cytokines, IL-2, IL-15 and to a lesser extent IL-7, induce FOXP3 up-regulation in vitro in activated human Teff cells. In contrast, cytokines which do not activate STAT5, such as IL-4 or transforming growth factor-β alone, do not directly induce FOXP3 expression in activated Teff cells. Moreover, expression of a constitutively active form of STAT5a is sufficient to induce FOXP3 expression in Teff cells. Expression of FOXP3 in activated Teff cells requires both TCR-mediated activation and endogenous IL-2, but is not dependent on cell division and does not induce suppressive function. The presence of STAT5-activating cytokines is also required to maintain high FOXP3 expression and suppressive activity of Treg cells in vitro. These data indicate that activation of STAT5 sustains FOXP3 expression in both Treg and Teff cells and contribute to our understanding of how cytokines affect the expression of FOXP3.

Original languageEnglish
Pages (from-to)421-431
Number of pages11
JournalInternational Immunology
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 2008

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Eragrostis
STAT5 Transcription Factor
Regulatory T-Lymphocytes
Cytokines
T-Lymphocytes
Interleukin-2
Interleukin-15
Interleukin-7
Transforming Growth Factors
Interleukin-4
Cell Division
Up-Regulation

Keywords

  • γ-Chain signaling cytokines
  • Suppressive activity
  • Transcription factor

ASJC Scopus subject areas

  • Immunology

Cite this

STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+ CD25- effector T cells. / Passerini, Laura; Allan, Sarah E.; Battaglia, Manuela; Di Nunzio, Sara; Alstad, Alicia N.; Levings, Megan K.; Roncarolo, Maria G.; Bacchetta, Rosa.

In: International Immunology, Vol. 20, No. 3, 03.2008, p. 421-431.

Research output: Contribution to journalArticle

Passerini, Laura ; Allan, Sarah E. ; Battaglia, Manuela ; Di Nunzio, Sara ; Alstad, Alicia N. ; Levings, Megan K. ; Roncarolo, Maria G. ; Bacchetta, Rosa. / STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+ CD25- effector T cells. In: International Immunology. 2008 ; Vol. 20, No. 3. pp. 421-431.
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