PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions.
Details
Serval ID
serval:BIB_976017D4D887
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions.
Journal
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
05/05/2021
Peer-reviewed
Oui
Volume
12
Number
1
Pages
2538
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
24/05/2021 13:40
Last modification date
12/01/2022 7:12