Abstract
Self-reactive T cells that escape negative selection in the thymus must be kept under control in the periphery. Intrinsic functional inactivation and mechanisms of dominant tolerance mediated by regulatory T cells exist to keep self-reactive T cells in check. Both systems are regulated by the activation of specific programmes of gene expression. Suboptimal stimulation of T cells results in the activation of a calcium-/nuclear factor of activated T cells (NFAT)-dependent cell-intrinsic programme of inactivation that, among other consequences, induces epigenetic changes in the interleukin (IL)-2 promoter that silence IL-2 expression and make T cells hypo-responsive to subsequent stimulation. Foxp3 directs the expression of set of genes that specify regulatory T cell development. In regulatory T cells, Foxp3 mediates activation and suppression of transcription of target genes by recruiting a multi-subunit complex involved in histone modification and chromatin remodelling.
| Original language | English (US) |
|---|---|
| Title of host publication | The Epigenetics of Autoimmune Diseases |
| Publisher | John Wiley and Sons |
| Pages | 1-20 |
| Number of pages | 20 |
| ISBN (Print) | 9780470758618 |
| DOIs | |
| State | Published - Apr 29 2009 |
Keywords
- Gene related to anergy in lymphocytes (GRAIL)
- Intercellular cell-adhesion molecule 1 (ICAM-1)
- Lymphocyte function-associated antigen-1 (LFA-1)
- Regulatory T cells (Tregs)
- T cell anergy, referring to cell-intrinsic mechanism
- T cell precursors
- T cell receptors (TCRs)
- Transcriptional regulation of T cell tolerance
- Treg cell-specific programme of gene expression
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology