Retinoids induce Fas(CD95) ligand cell surface expression via RARγ and nur77 in T cells

B. Tóth, Katalin Ludányi, Ildikó Kiss, Uwe Reichert, Serge Michel, L. Fésüs, Z. Szondy

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cells from the CD4+ murine T hybridoma line IP-12-7 enter the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon TCR stimulation. This stimulus regulates the sensitization of the Fas death pathway and the cell surface appearance of preformed FasL. The apoptosis is dependent on new mRNA and protein synthesis and involves upregulation of nur77. Two groupt of nuclear receptors for retinoic acids (RA) have been identified: retinoic acid receptors (RAR) and retinoid X receptors. IP-12-7 cells express RARα and RARγ. Here we show that, in the IP-12-7 T cells, RA also induced the expression and DNA binding of nur77, and the cell surface appearance of FasL. The induction was mediated via RARγ. Despite the induced expression of cell surface FasL, only two structurally related RARγ-selective compounds, CD437 and CD2325, initiated apoptosis in these cells. The lack of apoptosis induction by natural RA was related to the inability of RARγ to sensitize the Fas death-pathway. Cell surface FasL, however, was able to induce cell death in Fas-bearing target cells. Natural RA also induced the expression of FasL in phytohemagglutinin-activated peripheral murine T cells. It is proposed that therapeutically administered RA might induce apoptosis in Fas-sensitive cells via induction of FasL expression in activated T cells.

Original languageEnglish
Pages (from-to)827-836
Number of pages10
JournalEuropean Journal of Immunology
Volume34
Issue number3
DOIs
Publication statusPublished - Mar 2004

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Retinoic Acid Receptors
Fas Ligand Protein
Retinoids
T-Lymphocytes
Tretinoin
Apoptosis
Cell Death
Retinoid X Receptors
Hybridomas
Phytohemagglutinins
Cytoplasmic and Nuclear Receptors
Suicide
Up-Regulation
Messenger RNA
DNA

Keywords

  • Apoptosis
  • Fas ligand
  • nur77
  • Retinoid
  • T cell

ASJC Scopus subject areas

  • Immunology

Cite this

Retinoids induce Fas(CD95) ligand cell surface expression via RARγ and nur77 in T cells. / Tóth, B.; Ludányi, Katalin; Kiss, Ildikó; Reichert, Uwe; Michel, Serge; Fésüs, L.; Szondy, Z.

In: European Journal of Immunology, Vol. 34, No. 3, 03.2004, p. 827-836.

Research output: Contribution to journalArticle

Tóth, B. ; Ludányi, Katalin ; Kiss, Ildikó ; Reichert, Uwe ; Michel, Serge ; Fésüs, L. ; Szondy, Z. / Retinoids induce Fas(CD95) ligand cell surface expression via RARγ and nur77 in T cells. In: European Journal of Immunology. 2004 ; Vol. 34, No. 3. pp. 827-836.
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