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

Authors :
Stéphanie Bessoles
Daniel T. Utzschneider
Anh Thu Dang
Kristina Ludigs
Camilla Jandus
Pedro Romero
Eric Vivier
Greta Guarda
Dietmar Zehn
Werner Held
Giorgia Rota
Francesco Staehli
Wilson Castro
Centre d'Immunologie de Marseille - Luminy (CIML)
Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
European Project: 310890,EC:FP7:ERC,ERC-2012-StG_20111109,TRANSCRIPTIONALNLRS(2013)
European Project: 268537,EC:FP7:ERC,ERC-2010-AdG_20100317,THINK(2011)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Source :
Nature Communications, vol. 7, pp. 10554, Nature Communications, Vol. 7 (2016) P. 10554, Nature communications, Nature Communications, Nature Communications, Nature Publishing Group, 2016, 7, ⟨10.1038/ncomms10554⟩, Nature Communications, 2016, 7, ⟨10.1038/ncomms10554⟩, Nature Communications, Vol 7, Iss 1, Pp 1-10 (2016)
Publication Year :
2016

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.<br />NK cell tolerance to self-MHCI levels is calibrated during their development. Here the authors show that this tolerance is overcome by an inflammatory environment and that NLRC5 protects T cells from NK cell-mediated elimination by maintaining high MHCI expression.

Subjects

Subjects :
0301 basic medicine
Receptor expression
T-Lymphocytes
Interferon Inducers/toxicity
Self Tolerance/immunology
General Physics and Astronomy
Inbred C57BL
Transgenic
Interleukin 21
Mice
Congenic
Animals, Congenic
NLRC5
Chlorocebus aethiops
Killer Cells
Lymphocytic choriomeningitis virus
Mice, Knockout
education.field_of_study
Multidisciplinary
Interferon inducer
biology
Reverse Transcriptase Polymerase Chain Reaction
Intracellular Signaling Peptides and Proteins
Flow Cytometry
Animals
Arenaviridae Infections/immunology
Cercopithecus aethiops
Gene Expression Regulation/immunology
Histocompatibility Antigens Class I/genetics
Histocompatibility Antigens Class I/immunology
Humans
Inflammation/chemically induced
Inflammation/immunology
Intracellular Signaling Peptides and Proteins/genetics
Intracellular Signaling Peptides and Proteins/immunology
Killer Cells, Natural/immunology
Mice, Inbred C57BL
Mice, Transgenic
Poly I-C/toxicity
Spleen/cytology
Spleen/immunology
T-Lymphocytes/drug effects
T-Lymphocytes/immunology
Vero Cells
Histocompatibility Antigens Class I/genetics/immunology
Killer Cells, Natural
Self Tolerance
[SDV.IMM]Life Sciences [q-bio]/Immunology
medicine.symptom
Interferon Inducers
Inflammation/chemically induced/immunology
Science
Knockout
Population
Inflammation
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
MHC class I
medicine
Arenaviridae Infections
education
Histocompatibility Antigens Class I
General Chemistry
Intracellular Signaling Peptides and Proteins/genetics/immunology
030104 developmental biology
Poly I-C
Gene Expression Regulation
Natural/immunology
Immunology
biology.protein
Spleen/cytology/immunology
T-Lymphocytes/drug effects/immunology
CD8
Spleen

Details

Language :
English
ISSN :
20411723
Database :
OpenAIRE
Journal :
Nature Communications, vol. 7, pp. 10554, Nature Communications, Vol. 7 (2016) P. 10554, Nature communications, Nature Communications, Nature Communications, Nature Publishing Group, 2016, 7, ⟨10.1038/ncomms10554⟩, Nature Communications, 2016, 7, ⟨10.1038/ncomms10554⟩, Nature Communications, Vol 7, Iss 1, Pp 1-10 (2016)
Accession number :
edsair.doi.dedup.....0b283bf30cc22e75c68af1b8d0270f7e
Full Text :
https://doi.org/10.1038/ncomms10554⟩