6533b829fe1ef96bd128a38e
RESEARCH PRODUCT
The receptor NLRP3 is a transcriptional regulator of TH2 differentiation.
Cédric RébéEtienne HumblinDieudonnée TogbeBernhard RyffelAngélique ChevriauxRomain BoidotEmeric LimagneArlette HammanFrançois GhiringhelliFanny ChalminValentin DerangèreLionel ApetohMélanie BruchardHélène BergerFrédérique Végransubject
CD4-Positive T-LymphocytesInflammasomesImmunologyBlotting WesternBiologyInterleukin 21MiceTh2 CellsCell Line TumorNLR Family Pyrin Domain-Containing 3 ProteinImmunology and AllergyCytotoxic T cellAnimalsIL-2 receptorPromoter Regions GeneticInterleukin 3Oligonucleotide Array Sequence AnalysisMice KnockoutCD40integumentary systemReverse Transcriptase Polymerase Chain ReactionZAP70Gene Expression ProfilingCell DifferentiationNeoplasms ExperimentalAsthmaCell biologyGene Expression Regulation NeoplasticMice Inbred C57BLInterleukin 10Interferon Regulatory FactorsInterleukin 12biology.proteinNIH 3T3 CellsTrans-ActivatorsFemaleInterleukin-4Carrier ProteinsProtein BindingSignal Transductiondescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-06-22 | Nature immunology |