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

Ludigs, Kristina
Utzschneider, Daniel T
Staehli, Francesco
Bessoles, Stéphanie
Dang, Anh Thu
Rota, Giorgia
Castro, Wilson
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Published in Nature Communications. 2016, vol. 7, p. 10554
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 AnimalsAnimalsCongenicArenaviridae Infections/immunologyChlorocebus aethiopsFlow CytometryGene Expression Regulation/immunologyHistocompatibility Antigens Class I/genetics/immunologyHumansInflammation/chemically induced/immunologyInterferon Inducers/toxicityIntracellular Signaling Peptides and Proteins/genetics/immunologyKiller CellsNatural/immunologyLymphocytic choriomeningitis virusMiceMiceInbred C57BLMiceKnockoutMiceTransgenicPoly I-C/toxicityReverse Transcriptase Polymerase Chain ReactionSelf Tolerance/immunologySpleen/cytology/immunologyT-Lymphocytes/drug effects/immunologyVero Cells
PMID: 26861112
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Article (Published version) (763 Kb) - public document Free access
Research group Ciblage des lymphocytes sécrétant des cytokines (1015)
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LUDIGS, Kristina et al. NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions. In: Nature Communications, 2016, vol. 7, p. 10554. doi: 10.1038/ncomms10554

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Deposited on : 2020-03-17

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