The receptor NLRP3 is a transcriptional regulator of TH2 differentiation.
Mélanie BruchardCédric RebéValentin DerangèreDieudonnée TogbéBernhard RyffelRomain BoidotEtienne HumblinArlette HammanFanny ChalminHélène BergerAngélique ChevriauxEmeric LimagneLionel ApetohFrédérique VégranFrançois GhiringhelliPublished in: Nature immunology (2015)
The receptor NLRP3 is involved in the formation of the NLRP3 inflammasome that activates caspase-1 and mediates the release of interleukin 1β (IL-1β) and IL-18. Whether NLRP3 can shape immunological function independently of inflammasomes is unclear. We found that NLRP3 expression in CD4(+) T cells specifically supported a T helper type 2 (TH2) transcriptional program in a cell-intrinsic manner. NLRP3, but not the inflammasome adaptor ASC or caspase-1, positively regulated a TH2 program. In TH2 cells, NLRP3 bound the Il4 promoter and transactivated it in conjunction with the transcription factor IRF4. Nlrp3-deficient TH2 cells supported melanoma tumor growth in an IL-4-dependent manner and also promoted asthma-like symptoms. Our results demonstrate the ability of NLRP3 to act as a key transcription factor in TH2 differentiation.
Keyphrases
- nlrp inflammasome
- transcription factor
- induced apoptosis
- cell death
- gene expression
- cell cycle arrest
- dna binding
- chronic obstructive pulmonary disease
- dna methylation
- dendritic cells
- signaling pathway
- binding protein
- regulatory t cells
- oxidative stress
- cell proliferation
- immune response
- mesenchymal stem cells
- heat stress