PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_976017D4D887
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions.
Périodique
Nature communications
Auteur⸱e⸱s
Ercolano G., Gomez-Cadena A., Dumauthioz N., Vanoni G., Kreutzfeldt M., Wyss T., Michalik L., Loyon R., Ianaro A., Ho P.C., Borg C., Kopf M., Merkler D., Krebs P., Romero P., Trabanelli S., Jandus C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
05/05/2021
Peer-reviewed
Oui
Volume
12
Numéro
1
Pages
2538
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Mots-clé
Animals, Asthma, Cytokines/pharmacology, Gene Knockdown Techniques, Humans, Hypersensitivity, Immunity, Innate/immunology, Immunotherapy, Interleukin-33/metabolism, Lymphocytes/drug effects, Lymphocytes/metabolism, Mice, Mice, Inbred C57BL, Mitochondria, Neoplasms/pathology, Neoplasms/therapy, PPAR gamma/genetics, PPAR gamma/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/05/2021 14:40
Dernière modification de la notice
12/01/2022 8:12
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