Il11ra1-flox Mouse

Il11ra1, encoding the interleukin-11 receptor subunit alpha-1, is crucial for interleukin-11 (IL-11) signaling. IL-11 is a pro-inflammatory cytokine of the IL-6 family, and Il11ra1 enables IL-11 to regulate pathways like ERK-AMPK-mTORC1, which are important for cellular, tissue-and organismal-level functions and are associated with ageing, metabolism, and fibrosis-related processes [1,2,3,4,5,6,7,8].

In mouse models, deletion of Il11ra1 has shown protective effects in multiple disease conditions. In aged mice, Il11ra1 deletion protects against metabolic decline, multi-morbidity, and frailty [1]. In models of non-alcoholic steatohepatitis (NASH), Il11ra1 -/- mice had reduced steatosis, fibrosis, and inflammation compared to wild-type mice [3]. In the bleomycin mouse model of pulmonary fibrosis, Il11ra1-deleted mice, whose lung fibroblasts are unresponsive to profibrotic stimulation, are protected from fibrosis [4]. In cardiovascular fibrosis, genetic deletion of Il11ra1 protects against heart and kidney fibrosis and organ failure [5]. In hepatocyte-specific models, deletion of Il11ra1 protects against liver steatosis, fibrosis, and inflammation in NASH models [6]. In acute and chronic kidney disease models, mice with TEC-specific deletion of Il11ra1 have reduced pathogenic signaling and are protected from renal injury-induced inflammation, fibrosis, and failure [7]. In acetaminophen-induced liver injury, hepatocyte-specific deletion of Il11ra1 protects against liver injury [8]. Also, nanoparticle-mediated RNA interference targeting Il11ra1 effectively inhibits HSC activation and resolves fibrosis and inflammation in NASH models [9].

In conclusion, Il11ra1 is essential for IL-11-mediated signaling. The use of Il11ra1 gene-knockout (KO) and conditional-knockout (CKO) mouse models has revealed its significant role in various disease conditions such as ageing-related pathologies, NASH, pulmonary fibrosis, cardiovascular fibrosis, and kidney diseases. These findings suggest that targeting Il11ra1 or the IL-11/Il11ra1 axis could be a potential therapeutic strategy for treating these fibrotic and age-related diseases.