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- W4313405781 abstract "Abstract Cannabinoids modulate the activation of immune cells and physiological processes in the lungs. Group 2 innate lymphoid cells (ILC2)s are central players in type-2 asthma, but how cannabinoids modulate ILC2 activation remains to be elucidated. Using a combination of cannabinoid receptor (CB)2 KO mice, a CB2 antagonist and agonist, we here provide evidence that CB2 signaling in ILC2s is important for the development of ILC2-driven airway inflammation in both mice and human. We show that both naïve and activated murine pulmonary ILC2s express CB2. CB2 signaling did not affect ILC2 homeostasis at steady state, but strikingly stimulated ILC2 proliferation and function upon activation using various models of airway inflammation including IL-33, IL-25 and Alternaria alternata. As a result, ILC2s lacking CB2 induced lower lung inflammation, as we made similar observations using a CB2 antagonist. Conversely, CB2 agonism remarkably exacerbated ILC2-driven airway hyperreactivity and lung inflammation. Mechanistically, transcriptomic and protein analysis revealed that CB2 signaling induced CREB phosphorylation in ILC2s. Human ILC2s expressed CB2, as CB2 antagonism and agonism showed opposing effects on ILC2 effector function and development of airway hyperreactivity in humanized mice. Collectively, our results define CB2 signaling in ILC2s as an important modulator of airway inflammation. Furthermore, our findings highlight the stimulatory capacity of cannabinoids on ILC2s and offer new therapeutic avenues, including the use of substances or pathways able to modulate CB2 and capable of alleviating lung function in patients with lung inflammation." @default.
- W4313405781 created "2023-01-06" @default.
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- W4313405781 date "2022-05-01" @default.
- W4313405781 modified "2023-10-16" @default.
- W4313405781 title "CB2 engagement enhances group 2 innate lymphoid cell expansion and induction of airway hyperreactivity" @default.
- W4313405781 doi "https://doi.org/10.4049/jimmunol.208.supp.109.14" @default.
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