Activation-induced apoptosis and cell surface expression of Fas (CD95) ligand are reciprocally regulated by retinoic acid receptor α and γ and involve nur77 in T cells

Tóth, Réka; Szegezdi, Éva; Reichert, Uwe; Bernardon, Jean-Michel; Michel, Serge; Ancian, Philippe; Kis-Tóth, Katalin; Macsári, Zsolt; Fésüs, László; Szondy, Zsuzsa

doi:10.1002/1521-4141(200105)31:5<1382::aid-immu1382>3.0.co;2-y

Cited by 27 publications

(29 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies in our laboratory have shown that ligation of RAR § inhibits TCR-induced FasL expression and apoptosis by interfering with the transcriptional activity of nur77, whereas ligation of RAR + promotes TCRmediated apoptosis via enhancing the TCR-induced expression of nur77 [13]. While performing these studies, we observed that ligation of RAR + by RAR + -selective agonists alone could induce the expression of nur77 and FasL in Jurkat cells [13].…”

Section: Introductionsupporting

confidence: 47%

“…After the discovery of nuclear retinoid receptors and their ligands, and the demonstration of the expression of RAR § and RAR + in T cells [12,24], suggestions have been made that the active metabolites of vitamin A that mediate its effects on the immune system are the RA, including all-trans RA and 9-cis RA [25]. Indeed, RA were shown to promote T cell proliferation [24], and to affect apoptosis of T cells at various stages of their differentiation [12][13][14][15][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

“…Since we have previously observed that ligation of RAR + resulted in induction of nur77 in the human Jurkat T cells [13], we decided to investigate whether ligation of RAR + leads to increased expression of nur77 in the IP-12-7 T hybridoma cells as well, and whether its induction correlates with the apoptosis-inducing capability of the retinoids tested. To our surprise, all the five retinoids tested at a concentration of 300 nM were able to induce the expression of nur77 (Fig.…”

Section: Ligation Of Rar Q Induces the Expression Of Nur77 In Ip-12-7mentioning

confidence: 99%

“…While performing these studies, we observed that ligation of RAR + by RAR + -selective agonists alone could induce the expression of nur77 and FasL in Jurkat cells [13]. Since we have shown previously that ligation of RAR + by either natural or synthetic retinoids can induce apoptosis in thymocytes [12], we decided to investigate whether retinoids could also induce apoptosis in mature T cells, and whether this is related to the induced expression of nur77.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that T cells express RAR § and + [12][13][14], and retinoids can modulate the TCRmediated death of T lymphocytes [13][14][15]. For some of these studies, the human Jurkat T cells and IP-12-7 cells (a CD4 + murine T cell hybridoma that is specific for influenza hemagglutinin) [16] were used; both cell lines die in a manner dependent on Fas ligand (FasL / CD95) and Fas following TCR stimulation.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

et al. 2004

Self Cite

View full text Add to dashboard Cite

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 groups of nuclear receptors for retinoic acids (RA) have been identified: retinoic acid receptors (RAR) and retinoid X receptors. IP-12-7 cells express RAR § and RAR + . 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 RAR + . Despite the induced expression of cell surface FasL, only two structurally related RAR + -selective compounds, CD437 and CD2325, initiated apoptosis in these cells. The lack of apoptosis induction by natural RA was related to the inability of RAR + 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.

show abstract

Section: Introductionsupporting

confidence: 47%