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Scientific article
Open access
English

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

Published inNature Communications, vol. 12, no. 1, 2538
Publication date2021
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.

Funding
  • Swiss National Science Foundation - PRIMA PR00P3_179727
Citation (ISO format)
ERCOLANO, Giuseppe et al. PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions. In: Nature Communications, 2021, vol. 12, n° 1, p. 2538. doi: 10.1038/s41467-021-22764-2
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ISSN of the journal2041-1723
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Creation05/07/2021 3:45:00 PM
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