Scientific article
Open access

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

Published inNature Communications, vol. 7, 10554
Publication date2016

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.

  • Animals
  • Animals
  • Congenic
  • Arenaviridae Infections/immunology
  • Chlorocebus aethiops
  • Flow Cytometry
  • Gene Expression Regulation/immunology
  • Histocompatibility Antigens Class I/genetics/immunology
  • Humans
  • Inflammation/chemically induced/immunology
  • Interferon Inducers/toxicity
  • Intracellular Signaling Peptides and Proteins/genetics/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/immunology
  • T-Lymphocytes/drug effects/immunology
  • Vero Cells
Affiliation Not a UNIGE publication
Citation (ISO format)
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
Main files (1)
Article (Published version)
ISSN of the journal2041-1723

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