title: The receptor NLRP3 is a transcriptional regulator of TH2 differentiation.
abstract: 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.
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bruchard
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Rebé
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Derangère
authors.affiliation: Artimmune, Orleans, France.
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbé
authors.affiliation: Laboratory of Experimental and Molecular Immunology and Neurogenetics, UMR 7355 CNRS-University of Orleans, Orleans, France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Humblin
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Hamman
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Chalmin
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Berger
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Chevriaux
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Limagne
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: Lionel
authors.identifier: 000000022774438X
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Végran
authors.affiliation: 1] Inserm, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015534:Trans-Activators; D000099218:Interferon Regulatory Factor-4; C492716:Nlrp3 protein, mouse