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Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway

F Weih1, R P Ryseck, L Chen

  • 1Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 28, 1996
PubMed

Insights

The orphan nuclear receptor Nur77/N10 triggers T cell apoptosis by upregulating Fas ligand (FasL) in transgenic mice. This FasL upregulation leads to increased Fas signaling, causing thymocyte reduction, particularly in double-positive cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The orphan nuclear receptor Nur77/N10 is implicated in T cell hybridoma apoptosis.
  • Understanding Nur77/N10's role in thymocyte development is crucial for T cell homeostasis.

Purpose of the Study:

  • To investigate the impact of chronic Nur77/N10 expression on thymocyte populations in transgenic mice.
  • To elucidate the molecular mechanisms underlying Nur77/N10-induced apoptosis in thymocytes.

Main Methods:

  • Generation of Nur77/N10 transgenic mice.
  • Analysis of thymocyte subpopulations using flow cytometry.
  • Assessment of Fas ligand (FasL) and Fas receptor (Fas) expression levels.
  • Utilizing the gld/gld mouse model to study FasL-dependent apoptosis.

Main Results:

  • Chronic Nur77/N10 expression led to apoptosis and a reduction in CD4+CD8+, CD4+CD8-, and CD4-CD8+ thymocytes.
  • Nur77/N10-transgenic thymocytes exhibited increased FasL expression but not Fas receptor levels.
  • Nur77/N10-transgenic mice on a gld/gld background showed restored thymocyte cellularity and subpopulation profiles.

Conclusions:

  • Nur77/N10-induced apoptosis in double-positive thymocytes is mediated by upregulation of FasL.
  • This FasL upregulation results in enhanced Fas signaling, contributing to thymocyte elimination.
  • Nur77/N10 plays a significant role in regulating thymocyte apoptosis through the FasL pathway.

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