Ercolano, GiuseppeGiuseppeErcolanoGomez-Cadena, AlejandraAlejandraGomez-CadenaDumauthioz, NinaNinaDumauthiozVanoni, GiuliaGiuliaVanoniKreutzfeldt, MarioMarioKreutzfeldtWyss, TaniaTaniaWyssMichalik, LilianeLilianeMichalikLoyon, RomainRomainLoyonIanaro, AngelaAngelaIanaroHo, Ping-ChihPing-ChihHoBorg, ChristopheChristopheBorgKopf, ManfredManfredKopfMerkler, DoronDoronMerklerKrebs, PhilippePhilippeKrebs0000-0003-4918-6654Romero, PedroPedroRomeroTrabanelli, SaraSaraTrabanelliJandus, CamillaCamillaJandus2024-09-022024-09-022021-05-05https://boris-portal.unibe.ch/handle/20.500.12422/42076Group 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.en600 - Technology::610 - Medicine & healtharticle10.48350/1563163395316010.1038/s41467-021-22764-2