1. NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions
- Author
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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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
- 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 - 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., 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.
- Published
- 2016
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