The intrinsic expression of NLRP3 in Th17 cells promotes their protumor activity and conversion into Tregs

Th17 cells can perform either regulatory or inflammatory functions depending on the cytokine microenvironment. These plastic cells can transdifferentiate into Tregs during inflammation resolution, in allogenic heart transplantation models, or in cancer through mechanisms that remain poorly understood. Here, we demonstrated that NLRP3 expression in Th17 cells is essential for maintaining their immunosuppressive functions through an inflammasome-independent mechanism. In the absence of NLRP3, Th17 cells produce more inflammatory cytokines (IFNγ, Granzyme B, TNFα) and exhibit reduced immunosuppressive activity toward CD8+ cells. Moreover, the capacity of NLRP3-deficient Th17 cells to transdifferentiate into Treg-like cells is lost. Mechanistically, NLRP3 in Th17 cells interacts with the TGF-β receptor, enabling SMAD3 phosphorylation and thereby facilitating the acquisition of immunosuppressive functions. Consequently, the absence of NLRP3 expression in Th17 cells from tumor-bearing mice enhances CD8 + T-cell effectiveness, ultimately inhibiting tumor growth.

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Publication Details

Journal
Cellular and Molecular Immunology
Published
2025-04-07
DOI
https://doi.org/10.1038/s41423-025-01281-y
Citations
21
Primary Topic
Inflammasome and immune disorders
Type
article
Field-Weighted Citation Impact
16.93

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article

The intrinsic expression of NLRP3 in Th17 cells promotes their protumor activity and conversion into Tregs

Christophe Hibos, Corentin Richard, Élise Jacquin, Bernhard Ryffel et al.
21 citations
Cellular and Molecular Immunology
Inflammasome and immune disorders
16.93
article

The intrinsic expression of NLRP3 in Th17 cells promotes their protumor activity and conversion into Tregs

Christophe Hibos, Corentin Richard, Élise Jacquin, Bernhard Ryffel, L. Mayea Milian, Romain Mary, Théo Accogli, Catherine Paul, Mannon Geindreau, François Ghiringhelli, Frédérique Végran, Romain Boidot, Antoine Bernard, Fanny Chalmin, Étienne Humblin, Sandy Chevrier, Lionel Apétoh, Mélanie Bruchard
article en
21 citations

Abstract

Th17 cells can perform either regulatory or inflammatory functions depending on the cytokine microenvironment. These plastic cells can transdifferentiate into Tregs during inflammation resolution, in allogenic heart transplantation models, or in cancer through mechanisms that remain poorly understood. Here, we demonstrated that NLRP3 expression in Th17 cells is essential for maintaining their immunosuppressive functions through an inflammasome-independent mechanism. In the absence of NLRP3, Th17 cells produce more inflammatory cytokines (IFNγ, Granzyme B, TNFα) and exhibit reduced immunosuppressive activity toward CD8+ cells. Moreover, the capacity of NLRP3-deficient Th17 cells to transdifferentiate into Treg-like cells is lost. Mechanistically, NLRP3 in Th17 cells interacts with the TGF-β receptor, enabling SMAD3 phosphorylation and thereby facilitating the acquisition of immunosuppressive functions. Consequently, the absence of NLRP3 expression in Th17 cells from tumor-bearing mice enhances CD8 + T-cell effectiveness, ultimately inhibiting tumor growth.

Cellular and Molecular ImmunologyVol. 22(5)
Université d'Orléans (FR), Indiana University Health (US), Centre National de la Recherche Scientifique (FR), Inserm (FR), École Pratique des Hautes Études (FR), Université de Bourgogne (FR), Université Paris Sciences et Lettres (FR), Centre Georges François Leclerc (FR), Immunologie et Neurogénétique Expérimentales et Moléculaires (FR), Indiana Cancer Consortium (US), Genomic and Immunotherapy Medical Institute (FR), Indiana University – Purdue University Indianapolis (US)
Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, Fondation de France, Université de Bourgogne, Ministère de l'Enseignement Supérieur et de la Recherche, Institut National Du Cancer
Good health and well-being
Openalex Percentile: Top 1%
Inflammasome and immune disorders
16.93
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