Murine Schnurri-2 is required for positive selection of thymocytes

Nat Immunol. 2001 Nov;2(11):1048-53. doi: 10.1038/ni728.

Abstract

A key step in T cell development involves the positive selection of cells that recognize antigen presented by self-major histocompatibility complex. Yet, the signals that are activated by T cell receptor engagement and lead to cell survival remain unclear. We show here that mice lacking the transcription factor Schnurri-2 (Shn-2), a large metal-finger protein, had severely defective positive selection of CD4+ and CD8+ cells. Drosophila Shn acts as a cofactor of Smad homolog and is required for Decapentaplegic signaling. Vertebrates have at least three Shn orthologs (Shn-1, Shn-2 and Shn-3), which are thought to act as nuclear targets in the bone morphogenetic protein-transforming growth factor-beta-activin signaling pathways. These data raised the possibility that the Smad-Shn-2 complex is involved in the thymic selection of T cells.

Publication types

  • Comparative Study

MeSH terms

  • Activins / physiology
  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation
  • Bone Morphogenetic Proteins / physiology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Clonal Deletion / physiology*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics
  • Epithelial Cells / cytology
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Radiation Chimera
  • Self Tolerance / physiology*
  • Signal Transduction
  • Smad4 Protein
  • Species Specificity
  • Spleen / immunology
  • Spleen / pathology
  • Stromal Cells / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology*
  • Thymus Gland / immunology
  • Thymus Gland / pathology*
  • Thymus Gland / transplantation
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Transcription Factors / physiology
  • Transforming Growth Factor beta / physiology

Substances

  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • HIVEP1 protein, human
  • HIVEP3 protein, human
  • Hivep3 protein, mouse
  • MAD protein, Drosophila
  • Med protein, Drosophila
  • NF-kappa B
  • Smad4 Protein
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • dpp protein, Drosophila
  • shn protein, Drosophila
  • Activins
  • HIVEP2 protein, human