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

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:

13 Jun 2021 03:09

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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