Il33-flox Mouse

Interleukin-33 (IL33) belongs to the IL-1 cytokine family. It is constitutively produced by structural and lining cells like fibroblasts, endothelial and epithelial cells, and is expressed in the cellular nucleus in several tissues [1,3]. Functioning as an alarmin, it is passively released during cell necrosis or tissue damage to alert the immune system. IL33 activates allergic-inflammation-related cells like eosinophils, basophils, etc. through its receptor ST2, playing important roles in type-2 innate immunity [1].

In mouse models of spontaneous breast cancer metastasis, IL33 is upregulated in metastases-associated fibroblasts. Targeting IL33 in vivo inhibits lung metastasis and immune cell recruitment, showing its role in facilitating breast cancer lung metastasis by modifying the immune microenvironment towards type 2 inflammation [2]. In pancreatic cancer, stromal IL33, whose expression is dependent on epithelial oncogenic KRAS, affects multiple components of the tumor microenvironment. Lack of stromal IL33 in compartment-specific IL33 knockout mice leads to increased CD8+ T-cell infiltration and reduced tumor growth, suggesting IL33 as a potential therapeutic target [4].

In conclusion, IL33 is a crucial cytokine in the IL-1 family, playing important roles in type-2 innate immunity. Model-based research, especially IL33 knockout mouse models, has revealed its significance in diseases such as breast and pancreatic cancer, highlighting its potential as a therapeutic target in these cancer areas.