NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions.

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Serval ID
serval:BIB_8FDEF0BFED69
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions.
Journal
Nature Communications
Author(s)
Ludigs K., Jandus C., Utzschneider D.T., Staehli F., Bessoles S., Dang A.T., Rota G., Castro W., Zehn D., Vivier E., Held W., Romero P., Guarda G.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
7
Pages
10554
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK-T-cell crosstalk, raising the question on whether NLRC5 specifically modulates this interaction. Here we show that NK cells from Nlrc5-deficient mice exhibit moderate alterations in inhibitory receptor expression and responsiveness. Interestingly, NLRC5 expression in T cells is required to protect them from NK-cell-mediated elimination upon inflammation. Using T-cell-specific Nlrc5-deficient mice, we show that NK cells surprisingly break tolerance even towards 'self' Nlrc5-deficient T cells under inflammatory conditions. Furthermore, during chronic LCMV infection, the total CD8(+) T-cell population is severely decreased in these mice, a phenotype reverted by NK-cell depletion. These findings strongly suggest that endogenous T cells with low MHCI expression become NK-cell targets, having thus important implications for T-cell responses in naturally or therapeutically induced inflammatory conditions.
Keywords
Animals, Animals, Congenic, Arenaviridae Infections/immunology, Cercopithecus aethiops, Flow Cytometry, Gene Expression Regulation/immunology, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class I/immunology, Humans, Inflammation/chemically induced, Inflammation/immunology, Interferon Inducers/toxicity, Intracellular Signaling Peptides and Proteins/genetics, Intracellular Signaling Peptides and Proteins/immunology, Killer Cells, Natural/immunology, Lymphocytic choriomeningitis virus, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Poly I-C/toxicity, Reverse Transcriptase Polymerase Chain Reaction, Self Tolerance/immunology, Spleen/cytology, Spleen/immunology, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Vero Cells
Pubmed
Web of science
Open Access
Yes
Create date
10/02/2016 17:42
Last modification date
20/08/2019 15:53
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