Ligation of retinoic acid receptor alpha regulates negative selection of thymocytes by inhibiting both DNA binding of nur77 and synthesis of bim.

Ligation of Retinoic Acid Receptor Regulates Negative Selection of Thymocytes by Inhibiting Both DNA Binding of nur77 and Synthesis of Bim

Cyclosporin A blocks apoptosis by inhibiting the DNA binding activity of the transcription factor Nur77.

Engagement of T-cell receptors (TCRs) on immature thymocytes by self-antigen-major histocompatibility complexes causes the death of self-reactive thymocytes via apoptosis, a phenomenon that establishes T-cell tolerance. Similarly, treatment of thymocytes with anti-TCR antibodies leads to TCR-mediated apoptosis, which can also be induced in T-cell hybridomas. TCR-mediated apoptosis in immature t...

Fas/Fas ligand pathway

The orphan nuclear receptor Nur77/N10 has recently been demonstrated to be involved in apoptosis of T cell hybridomas. We report here that chronic expression of Nur77/N10 in thymocytes of transgenic mice results in a dramatic reduction of CD4+CD8+ double-positive as well as CD4+CD8and CD4-CD8+ single-positive cell populations due to an early onset ofapoptosis. CD4-CD8double-negative and CD25+ p...

Ubiquitous Self-Antigen Thymocyte Clonal Deletion Induced by Differential Roles for Bim and Nur77 in

Negative selection, primarily mediated through clonal deletion of self-reactive thymocytes, is critical for establishing self-tolerance and preventing autoimmunity. Recent studies suggest that the molecular mechanisms of negative selection differ depending on the thymic compartment and developmental stage at which thymocytes are deleted. Using the physiological HY cd4 TCR transgenic model of ne...

During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain

Apoptosis accompanying negative selection is a central but poorly understood event in T cell development. The Nur77 nuclear steroid receptor and Bim, a proapoptotic BH3-only member of the Bcl-2 family, are two molecules implicated in this process. However, how they relate to each other and how Nur77 induces apoptosis remain unclear. In thymocytes, Nur77 has been shown to induce cell death throu...