Type I NKT-cell-mediated TNF-α is a positive regulator of NLRP3 inflammasome priming

Melvyn T Chow, Helene Duret, Daniel M. Andrews, Christelle Faveeuw, Andreas Möller, Mark J. Smyth, Christophe Paget

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

The NLRP3 inflammasome plays a crucial role in the innate immune response to pathogens and exogenous or endogenous danger signals. Its activity must be precisely and tightly regulated to generate tailored immune responses. However, the immune cell subsets and cytokines controlling NLRP3 inflammasome activity are still poorly understood. Here, we have shown a link between NKT-cell-mediated TNF-α and NLRP3 inflammasome activity. The NLRP3 inflammasome in APCs was critical to potentiate NKT-cell-mediated immune responses, since C57BL/6 NLRP3 inflammasome-deficient mice exhibited reduced responsiveness to α-galactosylceramide. Importantly, NKT cells were found to act as regulators of NLRP3 inflammasome signaling, as NKT-cell-derived TNF-α was required for optimal IL-1β and IL-18 production by myeloid cells in response to α-galactosylceramide, by acting on the NLRP3 inflammasome priming step. Thus, NKT cells play a role in the positive regulation of NLRP3 inflammasome priming by mediating the production of TNF-α, thus demonstrating another means by which NKT cells control early inflammation.

Original languageEnglish
Pages (from-to)2111-2120
Number of pages10
JournalEuropean Journal of Immunology
Volume44
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Inflammasome
  • Inflammation
  • NKT cell
  • TNF-α

Cite this