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