Fiche publication
Date publication
avril 2025
Journal
Cellular & molecular immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BERNARD Alain
,
Dr BOIDOT Romain
,
Pr GHIRINGHELLI François
,
Pr PAUL Catherine
,
Dr VEGRAN Frédérique
,
Dr BRUCHARD Mélanie
,
Dr CHALMIN Fanny
,
Dr JACQUIN Elise
Tous les auteurs :
Accogli T, Hibos C, Milian L, Geindreau M, Richard C, Humblin E, Mary R, Chevrier S, Jacquin E, Bernard A, Chalmin F, Paul C, Ryffel B, Apetoh L, Boidot R, Bruchard M, Ghiringhelli F, Vegran F
Lien Pubmed
Résumé
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.
Mots clés
Cancer Immunology, NLRP3, Th17 cells, Tregs, Tumor microenvironment
Référence
Cell Mol Immunol. 2025 04 7;:
