Selective requirement for c-Myc at an early stage of V(alpha)14i NKT cell development.

Détails

ID Serval
serval:BIB_9E567BED9818
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Selective requirement for c-Myc at an early stage of V(alpha)14i NKT cell development.
Périodique
Journal of immunology
Auteur(s)
Mycko M.P., Ferrero I., Wilson A., Jiang W., Bianchi T., Trumpp A., MacDonald H.R.
ISSN
1550-6606[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
182
Numéro
8
Pages
4641-4648
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Valpha14 invariant (Valpha14i) NKT cells are a subset of regulatory T cells that utilize a semi-invariant TCR to recognize glycolipids associated with monomorphic CD1d molecules. During development in the thymus, CD4(+)CD8(+) Valpha14i NKT precursors recognizing endogenous CD1d-associated glycolipids on other CD4(+)CD8(+) thymocytes are selected to undergo a maturation program involving sequential expression of CD44 and NK-related markers such as NK1.1. The molecular requirements for Valpha14i NKT cell maturation, particularly at early developmental stages, remain poorly understood. In this study, we show that CD4-Cre-mediated T cell-specific inactivation of c-Myc, a broadly expressed transcription factor with a wide range of biological activities, selectively impairs Valpha14i NKT cell development without perturbing the development of conventional T cells. In the absence of c-Myc, Valpha14i NKT cell precursors are blocked at an immature CD44(low)NK1.1(-) stage in a cell autonomous fashion. Residual c-Myc-deficient immature Valpha14i NKT cells appear to proliferate normally, cannot be rescued by transgenic expression of BCL-2, and exhibit characteristic features of immature Valpha14i NKT cells such as high levels of preformed IL-4 mRNA and the transcription factor promyelocytic leukemia zinc finger. Collectively our data identify c-Myc as a critical transcription factor that selectively acts early in Valpha14i NKT cell development to promote progression beyond the CD44(low)NK1.1(-) precursor stage.
Mots-clé
Animals, CD8-Positive T-Lymphocytes/immunology, Cyclin-Dependent Kinase Inhibitor p21/metabolism, Gene Expression Regulation/immunology, Haplotypes/immunology, Immunologic Memory/immunology, Interleukin-4/genetics, Interleukin-4/immunology, Mice, Mice, Transgenic, Natural Killer T-Cells/cytology, Natural Killer T-Cells/immunology, Phenotype, Proto-Oncogene Proteins c-bcl-2/genetics, Proto-Oncogene Proteins c-bcl-2/metabolism, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/metabolism, RNA, Messenger/genetics, Receptors, Antigen, T-Cell, alpha-beta/immunology, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/01/2010 15:29
Dernière modification de la notice
20/08/2019 15:04
Données d'usage