PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions.
Fiche publication
Date publication
mai 2021
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BORG Christophe, Dr LOYON Romain
Tous les auteurs :
Ercolano G, Gomez-Cadena A, Dumauthioz N, Vanoni G, Kreutzfeldt M, Wyss T, Michalik L, Loyon R, Ianaro A, Ho PC, Borg C, Kopf M, Merkler D, Krebs P, Romero P, Trabanelli S, Jandus C
Lien Pubmed
Résumé
Group 2 innate lymphoid cells (ILC2s) play a critical role in protection against helminths and in diverse inflammatory diseases by responding to soluble factors such as the alarmin IL-33, that is often overexpressed in cancer. Nonetheless, regulatory factors that dictate ILC2 functions remain poorly studied. Here, we show that peroxisome proliferator-activated receptor gamma (PPARγ) is selectively expressed in ILC2s in humans and in mice, acting as a central functional regulator. Pharmacologic inhibition or genetic deletion of PPARγ in ILC2s significantly impair IL-33-induced Type-2 cytokine production and mitochondrial fitness. Further, PPARγ blockade in ILC2s disrupts their pro-tumoral effect induced by IL-33-secreting cancer cells. Lastly, genetic ablation of PPARγ in ILC2s significantly suppresses tumor growth in vivo. Our findings highlight a crucial role for PPARγ in supporting the IL-33 dependent pro-tumorigenic role of ILC2s and suggest that PPARγ can be considered as a druggable pathway in ILC2s to inhibit their effector functions. Hence, PPARγ targeting might be exploited in cancer immunotherapy and in other ILC2-driven mediated disorders, such as asthma and allergy.
Référence
Nat Commun. 2021 05 5;12(1):2538