Nos2, also known as inducible nitric oxide synthase (i-NOS), is an enzyme that plays a central role in inflammatory reactions following infection or tissue damage [5]. It catalyzes the production of nitric oxide (NO) from L-arginine, and the NO produced can have both beneficial and detrimental actions. The regulation of NOS2 expression is complex and is associated with multiple immunometabolic signaling pathways. Genetic models, such as gene-knockout (KO) mice, are valuable tools for studying its functions.

In macrophage-related studies, NOS2 has been shown to have significant impacts. In inflammatory macrophages, LACC1 bridges NOS2 and polyamine metabolism, converting L-citrulline to L-ornithine, and LACC1 phenotypes require upstream NOS2 [1]. In tumor-associated macrophages, NOS2 can produce NO to provoke tumor cell death, but its activity can be compromised in the tumor microenvironment, with hypoxia and other factors attenuating its function [2]. In addition, NOS2 expression in cancer cells often predicts poor outcome, as NO mediates multiple oncogenic pathways [3]. In the context of psoriasis, IL-17 induces NOS2, and lower levels of NO drive psoriasis pathogenesis [4]. In a murine model of central nervous system tuberculosis, Nos2-/-mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human CNS-TB [6].

In conclusion, Nos2 is crucial in inflammatory responses and immunometabolism. Studies using Nos2 KO mouse models have provided insights into its role in various disease conditions, including inflammation-related diseases, cancer, and infectious diseases like CNS-TB. Understanding Nos2 functions can help develop new therapeutic strategies for these diseases.