title: NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions.
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.
authors: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors: Kristina
authors: K
authors: Ludigs
authors: Ludwig Center for Cancer Research of the University of Lausanne, Epalinges 1066, Switzerland.
authors: Camilla
authors: C
authors: Jandus
authors: Division of Allergology and Immunology, CHUV, University of Lausanne, Epalinges 1066, Switzerland.
authors: Daniel T
authors: DT
authors: Utzschneider
authors: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors: Francesco
authors: F
authors: Staehli
authors: Ludwig Center for Cancer Research of the University of Lausanne, Epalinges 1066, Switzerland.
authors: Stéphanie
authors: S
authors: Bessoles
authors: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors: Anh Thu
authors: AT
authors: Dang
authors: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors: Giorgia
authors: G
authors: Rota
authors: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors: Wilson
authors: W
authors: Castro
authors: Division of Allergology and Immunology, CHUV, University of Lausanne, Epalinges 1066, Switzerland.
authors: Dietmar
authors: D
authors: Zehn
authors: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, Inserm U1104, CNRS UMR7280, Marseille 13288, France.|Immunologie, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille 13385, France.
authors: Eric
authors: E
authors: Vivier
authors: Ludwig Center for Cancer Research of the University of Lausanne, Epalinges 1066, Switzerland.
authors: Werner
authors: http://orcid.org/0000-0003-3292-1536
authors: W
authors: Held
authors: Ludwig Center for Cancer Research of the University of Lausanne, Epalinges 1066, Switzerland.
authors: Pedro
authors: P
authors: Romero
authors: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors: Greta
authors: G
authors: Guarda
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001117:Arenaviridae Infections / Q000276:immunology; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D007369:Interferon Inducers / Q000633:toxicity; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011070:Poly I-C / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014709:Vero Cells
chemical_list: D015395:Histocompatibility Antigens Class I; D007369:Interferon Inducers; D047908:Intracellular Signaling Peptides and Proteins; C549161:NLRC5 protein, mouse; D011070:Poly I-C