NLRC5 limits the activation of inflammatory pathways

Sz. Benkő, Joao G. Magalhaes, Dana J. Philpott, Stephen E. Girardin

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Nod-like receptors (NLRs) are intracellular sentinel proteins that are implicated in the detection of microbes and danger signals, thereby controlling several key innate immune pathways. The human genome encodes 22 NLR proteins, the function of many of which remains unknown. In this study, we present the identification and characterization of NLRC5, a NLR protein whose expression is found predominantly in cells of the myeloid and lymphoid lineages. NLRC5 expression was strongly induced by IFN-γ and more modestly by LPS and polyinosinic:polycytidylic acid. Overexpression of NLRC5 in HEK293T cells resulted in a global dampening of NF-κB-, AP-1-, and type I IFN-dependent signaling, most likely through transcriptional repression. Accordingly, NLRC5 was found to shuttle between the cytosol and the nucleus in a CrmA-dependent manner. Knocking down NLRC5 expression in RAW264.7 murine macrophages resulted in a potent upregulation of the proinflammatory responses to IFN-γ and LPS, including increased secretion of TNF, IL-6, and IL-1β, as well as cell surface expression of CD40. Strikingly, NLRC5 expression was also found to be critical for LPS-induced IL-10 production in RAW264.7 macrophages. Collectively, our results identify NLRC5 as a negative modulator of inflammatory pathways.

Original languageEnglish
Pages (from-to)1681-1691
Number of pages11
JournalJournal of Immunology
Volume185
Issue number3
DOIs
Publication statusPublished - Aug 1 2010

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Macrophages
Poly I-C
Proteins
Transcription Factor AP-1
Human Genome
Myeloid Cells
Interleukin-1
Interleukin-10
Cytosol
Interleukin-6
Up-Regulation
Lymphocytes
cyhalothrin

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Benkő, S., Magalhaes, J. G., Philpott, D. J., & Girardin, S. E. (2010). NLRC5 limits the activation of inflammatory pathways. Journal of Immunology, 185(3), 1681-1691. https://doi.org/10.4049/jimmunol.0903900

NLRC5 limits the activation of inflammatory pathways. / Benkő, Sz.; Magalhaes, Joao G.; Philpott, Dana J.; Girardin, Stephen E.

In: Journal of Immunology, Vol. 185, No. 3, 01.08.2010, p. 1681-1691.

Research output: Contribution to journalArticle

Benkő, S, Magalhaes, JG, Philpott, DJ & Girardin, SE 2010, 'NLRC5 limits the activation of inflammatory pathways', Journal of Immunology, vol. 185, no. 3, pp. 1681-1691. https://doi.org/10.4049/jimmunol.0903900
Benkő, Sz. ; Magalhaes, Joao G. ; Philpott, Dana J. ; Girardin, Stephen E. / NLRC5 limits the activation of inflammatory pathways. In: Journal of Immunology. 2010 ; Vol. 185, No. 3. pp. 1681-1691.
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