• A Corrigendum to this article was published on 18 November 2015

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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.

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  • 12 October 2015

    In the version of this article initially published, reference 44 (Farrell, G.A. Responding to aggression; the role of significant others for student psychiatric nurses, an ethnographic study. Nurse Educ. Today 9, 335–340 (1989)) was incorrect. The correct reference is as follows: Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787–795 (2012). The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank V. Petrilli (INSERM 1052) for BALB/c Nlrp3−/− mice. Supported by the French National Research Agency (“Investissements d'Avenir” program; ANR-11-LABX-0021), the Ligue nationale contre le cancer (F.G. and F.V.), the Fondation de France (L.A.), the Institut National du Cancer (F.G.), the Fondation ARC (L.A.), the Conseil Régional de Bourgogne/INSERM (H.B.), the Centre National de la Recherche Scientifique, Fonds Européen de Développement Économique et Régional, Le Stadium, Orléans and Fondation pour la Recherche Médicale (F.G. and B.R.), the French National Research Agency (ANR-13-JSV3-0001 to L.A.), the Fondation pour l'aide à la Recherche sur la Sclérose en Plaques (L.A. and M.D.), the Ligue Régionale contre le cancer Comité Grand-Est (L.A.) and the European Commission (PCIG10-GA-2011-303719 to L.A.).

Author information

Author notes

    • Frédérique Végran
    •  & François Ghiringhelli

    These authors jointly directed this work.

Affiliations

  1. Inserm, U866, Dijon, France.

    • Mélanie Bruchard
    • , Cédric Rebé
    • , Valentin Derangère
    • , Romain Boidot
    • , Etienne Humblin
    • , Arlette Hamman
    • , Fanny Chalmin
    • , Hélène Berger
    • , Angélique Chevriaux
    • , Emeric Limagne
    • , Lionel Apetoh
    • , Frédérique Végran
    •  & François Ghiringhelli
  2. Faculté de Médecine, Université de Bourgogne, Dijon, France.

    • Mélanie Bruchard
    • , Cédric Rebé
    • , Valentin Derangère
    • , Romain Boidot
    • , Etienne Humblin
    • , Arlette Hamman
    • , Fanny Chalmin
    • , Hélène Berger
    • , Angélique Chevriaux
    • , Emeric Limagne
    • , Lionel Apetoh
    • , Frédérique Végran
    •  & François Ghiringhelli
  3. Centre Georges François Leclerc, Dijon, France.

    • Cédric Rebé
    • , Valentin Derangère
    • , Romain Boidot
    • , Angélique Chevriaux
    • , Lionel Apetoh
    • , Frédérique Végran
    •  & François Ghiringhelli
  4. Artimmune, Orleans, France.

    • Dieudonnée Togbé
  5. Laboratory of Experimental and Molecular Immunology and Neurogenetics, UMR 7355 CNRS–University of Orleans, Orleans, France.

    • Bernhard Ryffel

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Contributions

M.B. did in vitro and in vivo experiments; C.R., V.D., A.H., F.C., H.B., A.C. and E.L. did in vitro experiments; D.T. and B.R. generated asthma experiments; R.B. performed and supervised the extraction, amplification and library preparation for RNA sequencing and ChIP-seq; E.H. did in vitro experiments; F.V. performed bioinformatics analysis; M.B., L.A., F.V. and F.G. supervised the study and wrote the manuscript; and F.G. conceived of and designed the study.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to François Ghiringhelli.

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    NRLP3 localization in Th1 cells

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    NRLP3 localization in Th2 cells

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DOI

https://doi.org/10.1038/ni.3202

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