Il1r1-flox Mouse

Il1r1, encoding interleukin 1 receptor type 1, is a key component in the interleukin 1 (IL-1) signaling pathway. The IL-1 pathway is a central mediator for systemic inflammation, and Il1r1 is crucial for IL-1 signaling, which is involved in numerous biological processes including inflammation, immune response, and metabolism [3].

In colorectal cancer, IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression. Fibroblast-specific IL1R1 knockout reduces tumor growth in vivo, accompanied by reduced intratumoral Th17 cell infiltration, suggesting its pro-tumorigenic role [1]. In obesity-related studies, IL1R1-deficient mice are completely resistant to the leptin-sensitizing and anti-obesity effects of celastrol, indicating that IL1R1 is a gatekeeper for celastrol's metabolic actions [2]. Also, a missense variant in IL1R1 in a patient with chronic recurrent multifocal osteomyelitis led to unopposed IL-1 signaling due to disrupted binding of the antagonist ligand. Mice with a homologous mutation showed similar hyperinflammation [3].

In conclusion, Il1r1 plays essential roles in inflammation, metabolism, and tumor-related processes. Studies using gene knockout mouse models, such as fibroblast-specific IL1R1 knockout in colorectal cancer and IL1R1-deficient mice in obesity research, have significantly enhanced our understanding of its functions in disease conditions, highlighting its potential as a therapeutic target in various diseases including cancer, auto-inflammatory diseases, and metabolic disorders.