huIL1RL1(IL33R) Mouse

The IL1RL1 gene, also known as ST2 or IL33R, encodes a member of the interleukin-1 receptor superfamily, specifically binding the cytokine IL-33, a key mediator of inflammation and immunity ^[1]. This gene produces two primary protein isoforms: transmembrane ST2L and soluble sST2. ST2L, the functional receptor, is expressed on immune cells, including mast cells, helper T cells, and eosinophils, as well as epithelial and endothelial cells ^[1]. Upon IL-33 binding, ST2L activation initiates NF-κB and MAPK inflammatory signaling cascades, leading to the release of cytokines and chemokines that drive type II inflammation, fibrosis, and tumor microenvironment modulation ^[1-4]. The IL-33/ST2 axis exhibits context-dependent functions in tumors, potentially promoting proliferation, metastasis, and angiogenesis, or conversely, activating anti-tumor immunity and suppressing tumor growth ^[2]. Polymorphisms in IL1RL1 have been associated with increased susceptibility to a range of diseases, including asthma, allergies, cardiovascular diseases, inflammatory bowel disease, and cancers ^[1-5]. Consequently, the IL-33/ST2 signaling pathway has emerged as a focus of intense research for therapeutic intervention in diverse pathologies, with IL1RL1 representing a potential target for the development of novel therapies for cancer, inflammatory, and immune-related diseases ^[1-5].

The huIL1RL1(IL33R) mouse is a humanized model constructed using gene editing technology, where the mouse IL1RL1 signal peptide and endogenous extracellular domain were replaced with the human IL1RL1 signal peptide and extracellular domain. The murine IL1RL1 transmembrane and cytoplasmic region were preserved. Homozygous huIL1RL1(IL33R) mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of cancer, inflammatory, and immune-related diseases, and for the development of IL1RL1-targeted drugs.