The receptor NLRP3 is a transcriptional regulator of TH2 differentiation

Mélanie Bruchard; Cédric Rebé; Valentin Derangère; Dieudonnée Togbé; Bernhard Ryffel; Romain Boidot; Etienne Humblin; Arlette Hamman; Fanny Chalmin; Hélène Berger; Angélique Chevriaux; Emeric Limagne; Lionel Apetoh; Frédérique Végran; François Ghiringhelli

doi:10.1038/ni.3202

The receptor NLRP3 is a transcriptional regulator of T_H2 differentiation

Mélanie Bruchard, Cédric Rebé, Valentin Derangère, Dieudonnée Togbé, Bernhard Ryffel, Romain Boidot, Etienne Humblin, Arlette Hamman, Fanny Chalmin, Hélène Berger, Angélique Chevriaux, Emeric Limagne, Lionel Apetoh, Frédérique Végran, François Ghiringhelli

Research output: Contribution to journal › Article › peer-review

270 Scopus citations

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 (T_H2) transcriptional program in a cell-intrinsic manner. NLRP3, but not the inflammasome adaptor ASC or caspase-1, positively regulated a T_H2 program. In T_H2 cells, NLRP3 bound the Il4 promoter and transactivated it in conjunction with the transcription factor IRF4. Nlrp3-deficient T_H2 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 T_H2 differentiation.

Original language	English
Pages (from-to)	859-870
Number of pages	12
Journal	Nature Immunology
Volume	16
Issue number	8
DOIs	https://doi.org/10.1038/ni.3202
State	Published - 21 Jul 2015
Externally published	Yes

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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.",

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AU - Bruchard, Mélanie

AU - Rebé, Cédric

AU - Derangère, Valentin

AU - Togbé, Dieudonnée

AU - Ryffel, Bernhard

AU - Boidot, Romain

AU - Humblin, Etienne

AU - Hamman, Arlette

AU - Chalmin, Fanny

AU - Berger, Hélène

AU - Chevriaux, Angélique

AU - Limagne, Emeric

AU - Apetoh, Lionel

AU - Végran, Frédérique

AU - Ghiringhelli, François

PY - 2015/7/21

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AB - 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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JO - Nature Immunology

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The receptor NLRP3 is a transcriptional regulator of TH2 differentiation

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The receptor NLRP3 is a transcriptional regulator of T_H2 differentiation