An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells.
Nat Immunol, 2010/3;11(3):240-9.
D'Cruz LM[1], Knell J, Fujimoto JK, Goldrath AW
Affiliations
PMID: 20154672DOI: 10.1038/ni.1845
Impact factor: 31.25
Abstract
E proteins are basic helix-loop-helix transcription factors that regulate many key aspects of lymphocyte development. Thymocytes express multiple E proteins that are thought to provide cooperative and compensatory functions crucial for T cell differentiation. Contrary to that, we report here that the E protein HEB was uniquely required at the CD4(+)CD8(+) double-positive (DP) stage of T cell development. Thymocytes lacking HEB showed impaired survival, failed to make rearrangements of variable-alpha (V(alpha)) segments to distal joining-alpha (J(alpha)) segments in the gene encoding the T cell antigen receptor alpha-chain (Tcra) and had a profound, intrinsic block in the development of invariant natural killer T cells (iNKT cells) at their earliest progenitor stage. Thus, our results show that HEB is a specific and essential factor in T cell development and in the generation of the iNKT cell lineage, defining a unique role for HEB in the regulation of lymphocyte maturation.
MeSH terms
Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell Survival; Chimera; Flow Cytometry; Gene Expression Regulation; Mice; Mice, Knockout; Mice, Transgenic; Natural Killer T-Cells; Oligonucleotide Array Sequence Analysis; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; Transcription, Genetic
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