NLRC5 deficiency selectively impairs MHC class I- dependent lymphocyte killing by cytotoxic T cells.

Détails

ID Serval
serval:BIB_98F298ABDC3E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
NLRC5 deficiency selectively impairs MHC class I- dependent lymphocyte killing by cytotoxic T cells.
Périodique
Journal of Immunology
Auteur(s)
Staehli F., Ludigs K., Heinz L.X., Seguín-Estévez Q., Ferrero I., Braun M., Schroder K., Rebsamen M., Tardivel A., Mattmann C., MacDonald H.R., Romero P., Reith W., Guarda G., Tschopp J.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2012
Volume
188
Numéro
8
Pages
3820-3828
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular proteins involved in innate-driven inflammatory responses. The function of the family member NLR caspase recruitment domain containing protein 5 (NLRC5) remains a matter of debate, particularly with respect to NF-κB activation, type I IFN, and MHC I expression. To address the role of NLRC5, we generated Nlrc5-deficient mice (Nlrc5(Δ/Δ)). In this article we show that these animals exhibit slightly decreased CD8(+) T cell percentages, a phenotype compatible with deregulated MHC I expression. Of interest, NLRC5 ablation only mildly affected MHC I expression on APCs and, accordingly, Nlrc5(Δ/Δ) macrophages efficiently primed CD8(+) T cells. In contrast, NLRC5 deficiency dramatically impaired basal expression of MHC I in T, NKT, and NK lymphocytes. NLRC5 was sufficient to induce MHC I expression in a human lymphoid cell line, requiring both caspase recruitment and LRR domains. Moreover, endogenous NLRC5 localized to the nucleus and occupied the proximal promoter region of H-2 genes. Consistent with downregulated MHC I expression, the elimination of Nlrc5(Δ/Δ) lymphocytes by cytotoxic T cells was markedly reduced and, in addition, we observed low NLRC5 expression in several murine and human lymphoid-derived tumor cell lines. Hence, loss of NLRC5 expression represents an advantage for evading CD8(+) T cell-mediated elimination by downmodulation of MHC I levels-a mechanism that may be exploited by transformed cells. Our data show that NLRC5 acts as a key transcriptional regulator of MHC I in lymphocytes and support an essential role for NLRs in directing not only innate but also adaptive immune responses.
Mots-clé
Adaptive Immunity, Animals, Antigen-Presenting Cells/cytology, Antigen-Presenting Cells/immunology, Bone Marrow/immunology, Cell Differentiation, Cell Line, Tumor, Cell Nucleus/genetics, Cell Nucleus/immunology, Cell Proliferation, Gene Expression Regulation, Genes, MHC Class I, Humans, Immunity, Innate, Intracellular Signaling Peptides and Proteins/genetics, Intracellular Signaling Peptides and Proteins/immunology, Killer Cells, Natural/cytology, Killer Cells, Natural/immunology, Macrophages/cytology, Macrophages/immunology, Mice, Mice, Knockout, NF-kappa B/genetics, NF-kappa B/immunology, T-Lymphocytes, Cytotoxic/cytology, T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/05/2012 16:06
Dernière modification de la notice
20/08/2019 16:00
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