NLRC5 deficiency selectively impairs MHC class idependent lymphocyte killing by cytotoxic T cells

Staehli, Francesco, Ludigs, Kristina, Heinz, Leonhard X., Seguin-Estevez, Queralt, Ferrero, Isabel, Braun, Marion, Schroder, Kate, Rebsamen, Manuele, Tardivel, Aubry, Mattmann, Chantal, MacDonald, H. Robson, Romero, Pedro, Reith, Walter, Guarda, Greta and Tschopp, Jurg (2012) NLRC5 deficiency selectively impairs MHC class idependent lymphocyte killing by cytotoxic T cells. Journal of Immunology, 188 8: 3820-3828. doi:10.4049/jimmunol.1102671

Author Staehli, Francesco
Ludigs, Kristina
Heinz, Leonhard X.
Seguin-Estevez, Queralt
Ferrero, Isabel
Braun, Marion
Schroder, Kate
Rebsamen, Manuele
Tardivel, Aubry
Mattmann, Chantal
MacDonald, H. Robson
Romero, Pedro
Reith, Walter
Guarda, Greta
Tschopp, Jurg
Title NLRC5 deficiency selectively impairs MHC class idependent lymphocyte killing by cytotoxic T cells
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2012-04-15
Sub-type Article (original research)
DOI 10.4049/jimmunol.1102671
Volume 188
Issue 8
Start page 3820
End page 3828
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2013
Language eng
Formatted abstract
Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular proteins involved in innate-driven inflammatory responses. The function of the family member NLR caspase recruitment domain containing protein 5 (NLRC5) remains a matter of debate, particularly with respect to NF-κB activation, type I IFN, and MHC I expression. To address the role of NLRC5, we generated Nlrc5-deficient mice (Nlrc5Δ/Δ). In this article we show that these animals exhibit slightly decreased CD8+ T cell percentages, a phenotype compatible with deregulated MHC I expression. Of interest, NLRC5 ablation only mildly affected MHC I expression on APCs and, accordingly, Nlrc5Δ/Δ macrophages efficiently primed CD8+ T cells. In contrast, NLRC5 deficiency dramatically impaired basal expression of MHC I in T, NKT, and NK lymphocytes. NLRC5 was sufficient to induce MHC I expression in a human lymphoid cell line, requiring both caspase recruitment and LRR domains. Moreover, endogenous NLRC5 localized to the nucleus and occupied the proximal promoter region of H-2 genes. Consistent with downregulated MHC I expression, the elimination of Nlrc5Δ/Δ lymphocytes by cytotoxic T cells was markedly reduced and, in addition, we observed low NLRC5 expression in several murine and human lymphoid-derived tumor cell lines. Hence, loss of NLRC5 expression represents an advantage for evading CD8+ T cell-mediated elimination by downmodulation of MHC I levels—a mechanism that may be exploited by transformed cells. Our data show that NLRC5 acts as a key transcriptional regulator of MHC I in lymphocytes and support an essential role for NLRs in directing not only innate but also adaptive immune responses.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 35 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 07 May 2012, 18:58:03 EST by System User on behalf of School of Chemistry & Molecular Biosciences