Ercolano, Giuseppe; Gomez-Cadena, Alejandra; Dumauthioz, Nina; Vanoni, Giulia; Kreutzfeldt, Mario; Wyss, Tania; Michalik, Liliane; Loyon, Romain; Ianaro, Angela; Ho, Ping-Chih; Borg, Christophe; Kopf, Manfred; Merkler, Doron; Krebs, Philippe; Romero, Pedro; Trabanelli, Sara; Jandus, Camilla (2021). PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions. Nature Communications, 12(1), p. 2538. Springer Nature 10.1038/s41467-021-22764-2
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology |
UniBE Contributor: |
Krebs, Philippe |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Philippe Krebs |
Date Deposited: |
08 Jun 2021 12:09 |
Last Modified: |
05 Dec 2022 15:51 |
Publisher DOI: |
10.1038/s41467-021-22764-2 |
PubMed ID: |
33953160 |
BORIS DOI: |
10.48350/156316 |
URI: |
https://boris.unibe.ch/id/eprint/156316 |
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