Ligation of RARγ inhibits proliferation of phytohaemagglutinin- stimulated T-cells via down-regulating JAK3 protein levels

Katalin Ludányi, Zsuzsanna S. Nagy, Magdolna Alexa, Uwe Reichert, Serge Michel, László Fésüs, Zsuzsa Szondy

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The mechanisms whereby Vitamin A regulates the immune system are poorly understood. We have shown previously that retinoic acids, the Vitamin A derivatives, promote both apoptosis of neglected thymocytes and the activation-induced cell death of peripheral T-cells via ligating the nuclear retinoid receptor (RAR) gamma. In the present study, we found that human peripheral T-cells express RARα and γ, but not RARβ. Increasing concentrations of 9-cis RA inhibited phytohaemagglutinin (PHA)-induced proliferation of T-cells, an effect that could be mimicked only by addition of RARγ agonists and could be inhibited by an RARγ antagonist. Interleukin-2 (IL-2) produced is known to mediate PHA-induced proliferation of T lymphocytes. Ligation of RARγ did not affect the PHA-induced high affinity IL-2 receptor expression, slightly reduced the PHA-induced IL-2 production, but interfered with the IL-2-mediated signal transduction resulting in inhibition of PHA-induced phosphorylation of retinoblastoma protein and of up-regulation of Bcl-2. Janus kinases JAK1 and JAK3 play a determinant role in IL-2-dependent signal transduction. Ligation of RARγ did not affect the levels of JAK1, but prevented IL-2-induced expression of JAK3 resulting in inhibition of PHA-induced phosphorylation of Stat5 molecules. Our data suggest that the previously observed toxic effect of high concentrations of retinoids on the immune system might be mediated via formation of 9-cis RA, which via ligation of RARγ not only induces cell death in immature thymocytes, but inhibits proliferation of T-cells as well.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalImmunology letters
Volume98
Issue number1
DOIs
Publication statusPublished - Apr 15 2005

Keywords

  • Bcl-2
  • Cellular proliferation
  • JAK3
  • Retinoids
  • Stat5

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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