Functional education of invariant NKT cells by dendritic cell tuning of SHP-1.

Détails

ID Serval
serval:BIB_DBDAC3C10AEC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Functional education of invariant NKT cells by dendritic cell tuning of SHP-1.
Périodique
Journal of Immunology
Auteur(s)
Napolitano A., Pittoni P., Beaudoin L., Lehuen A., Voehringer D., MacDonald H.R., Dellabona P., Casorati G.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2013
Volume
190
Numéro
7
Pages
3299-3308
Langue
anglais
Résumé
Invariant NKT (iNKT) cells play key roles in host defense by recognizing lipid Ags presented by CD1d. iNKT cells are activated by bacterial-derived lipids and are also strongly autoreactive toward self-lipids. iNKT cell responsiveness must be regulated to maintain effective host defense while preventing uncontrolled stimulation and potential autoimmunity. CD1d-expressing thymocytes support iNKT cell development, but thymocyte-restricted expression of CD1d gives rise to Ag hyperresponsive iNKT cells. We hypothesized that iNKT cells require functional education by CD1d(+) cells other than thymocytes to set their correct responsiveness. In mice that expressed CD1d only on thymocytes, hyperresponsive iNKT cells in the periphery expressed significantly reduced levels of tyrosine phosphatase SHP-1, a negative regulator of TCR signaling. Accordingly, heterozygous SHP-1 mutant mice displaying reduced SHP-1 expression developed a comparable population of Ag hyperresponsive iNKT cells. Restoring nonthymocyte CD1d expression in transgenic mice normalized SHP-1 expression and iNKT cell reactivity. Radiation chimeras revealed that CD1d(+) dendritic cells supported iNKT cell upregulation of SHP-1 and decreased responsiveness after thymic emigration. Hence, dendritic cells functionally educate iNKT cells by tuning SHP-1 expression to limit reactivity.
Mots-clé
Animals, Antigens, CD1d/genetics, Antigens, CD1d/metabolism, Cluster Analysis, Dendritic Cells/immunology, Dendritic Cells/metabolism, Gene Expression Profiling, Gene Expression Regulation, Genomic Imprinting, Humans, Hypersensitivity/genetics, Hypersensitivity/immunology, Mice, Mice, Knockout, Natural Killer T-Cells/immunology, Natural Killer T-Cells/metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism, Thymus Gland/immunology, Thymus Gland/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/05/2013 19:42
Dernière modification de la notice
20/08/2019 16:00
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