Arginine metabolism and the NF-ĸB pathway jointly regulate the airway inflammation in asthma mediated by ILC2s

Type 2 innate lymphoid cells (ILC2) are the key effector cells in airway inflammation of asthma. Arginase 2 (Arg2) and the NF-ĸB pathway are both involved in the inflammatory response, but the mechanism by which they jointly regulate the function of ILC2s remains unclear. In this study, an OVA-induced mouse asthma model was used, combined with in vivo and in vitro experiments, flow cytometry and targeted metabolomics to explore the roles of both and their mutual regulatory relationship. In OVA-induced asthmatic mice, airway inflammation was aggravated and the proportion of lung ILC2s increased, while Arg2 expression was upregulated and the NF-ĸB pathway was activated. In the in vivo experiments, the Arg2 inhibitor nor-NOHA or the NF-ĸB inhibitor DHMEQ could alleviate inflammation, and the combined treatment was more effective. Experiments in vitro have shown that NF-ĸB may promote the expression of Arg2, and inhibiting the expression of Arg2 can partially reduce the activation of the NF-ĸB pathway; combined inhibition can reduce the secretion of pro-inflammatory factors by ILC2s. Additionally, TNF-α could weaken the inhibitory effect of nor-NOHA on Arg2. In summary, NF-ĸB may regulate the expression of Arg2 in ILC2s, and Arg2 may feedback-regulate the NF-ĸB-mediated inflammation through arginine metabolism. The two synergistically affect the activation of ILC2s and the type 2 inflammation of asthma. Targeting both simultaneously can alleviate airway inflammation and provide a potential new idea for asthma treatment.