The receptor NLRP3 is a transcriptional regulator of TH2 differentiation.
Fiche publication
Date publication
août 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain, Pr GHIRINGHELLI François, Dr VEGRAN Frédérique, Dr REBE Cédric, Dr BRUCHARD Mélanie, Dr CHALMIN Fanny, Dr LIMAGNE Emeric, Dr DERANGERE Valentin
Tous les auteurs :
Bruchard M, Rebe C, Derangere V, Togbe D, Ryffel B, Boidot R, Humblin E, Hamman A, Chalmin F, Berger H, Chevriaux A, Limagne E, Apetoh L, Vegran F, Ghiringhelli F
Lien Pubmed
Résumé
The receptor NLRP3 is involved in the formation of the NLRP3 inflammasome that activates caspase-1 and mediates the release of interleukin 1beta (IL-1beta) 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.
Référence
Nat Immunol. 2015 Aug;16(8):859-70