Journal article
NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions
K Ludigs, C Jandus, DT Utzschneider, F Staehli, S Bessoles, AT Dang, G Rota, W Castro, D Zehn, E Vivier, W Held, P Romero, G Guarda
Nature Communications | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/ncomms10554
Open access
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. Furthermo..
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Awarded by Ligue Contre le Cancer
Funding Acknowledgements
We thank S. Chelbi, UNIL, Lausanne, Switzerland, D. Stojanovova, Charles University, Prague, Czech Republic, and Elisenda Alari Pahissa, Ludwig Center, Lausanne, for technical help and Jurg Tschopp for having contributed tools essential to this project. Studies in the group of G.G. are funded by the Swiss National Science Foundation (PP00P3_139094) and the European Research Council (ERC-2012-StG310890). E.V. lab is supported by the European Research Council (THINK Advanced Grant), the Ligue Nationale contre le Cancer (Equipe Labellisee) and by institutional grants from INSERM, CNRS and Aix-Marseille University to CIML. E.V. is a scholar of the Institut Universitaire de France.