GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis

Marie-Liesse Labat, Muriel David, Armelle Biola-Vidamment, Damiana Lecoeuche, Maria Christina Zennaro, Jacques Bertoglio, Marc Pallardy

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Interleukin-2 (IL-2) withdrawal is a physiologic process inducing cell death in activated T lymphocytes. Glucocorticoid-induced leucine zipper (GILZ) has recently been identified as a protein modulating T-cell receptor activation by repressing various signaling pathways. We report here that IL-2 deprivation leads to expression of GILZ in T lymphocytes. We then characterized the human gilz promoter and showed that FoxO3 (Forkhead box class O3) binding to the Forkhead responsive elements identified in the promoter is necessary for induction of gilz expression upon IL-2 withdrawal. To assess the functional consequences of this induction, we used 2 strategies, GILZ overexpression and GILZ silencing in murine IL-2-dependent CTLL-2 cells. GILZ overexpression protects CTLL-2 cells from IL-2 withdrawal-induced apoptosis, whereas cell death is accelerated in cells unable to express GILZ. Concomitantly, the expression of Bim is inhibited in GILZ-overexpressing cells and enhanced when GILZ expression is impaired. Furthermore, GILZ inhibits FoxO3 transcriptional activity that leads to inhibition of Bim expression but also to down-regulation of GILZ itself. Therefore, GILZ is a transiently expressed protein induced upon IL-2 withdrawal that protects T cells from the onset of apoptosis.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalBlood
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Leucine Zippers
T-cells
Glucocorticoids
Interleukin-2
Transcription Factors
Apoptosis
T-Lymphocytes
Cell death
Cell Death
T-Cell Antigen Receptor
Proteins
Down-Regulation
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Labat, M-L., David, M., Biola-Vidamment, A., Lecoeuche, D., Zennaro, M. C., Bertoglio, J., & Pallardy, M. (2004). GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. Blood, 104(1), 215-223. https://doi.org/10.1182/blood-2003-12-4295

GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. / Labat, Marie-Liesse; David, Muriel; Biola-Vidamment, Armelle; Lecoeuche, Damiana; Zennaro, Maria Christina; Bertoglio, Jacques; Pallardy, Marc.

In: Blood, Vol. 104, No. 1, 01.07.2004, p. 215-223.

Research output: Contribution to journalArticle

Labat, M-L, David, M, Biola-Vidamment, A, Lecoeuche, D, Zennaro, MC, Bertoglio, J & Pallardy, M 2004, 'GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis', Blood, vol. 104, no. 1, pp. 215-223. https://doi.org/10.1182/blood-2003-12-4295
Labat, Marie-Liesse ; David, Muriel ; Biola-Vidamment, Armelle ; Lecoeuche, Damiana ; Zennaro, Maria Christina ; Bertoglio, Jacques ; Pallardy, Marc. / GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. In: Blood. 2004 ; Vol. 104, No. 1. pp. 215-223.
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