Interleukin-33 (IL33) belongs to the IL-1 cytokine family. It is constitutively produced by structural and lining cells such as fibroblasts, endothelial cells, and epithelial cells of various tissues [1]. Unlike most cytokines, it is a nuclear cytokine that is passively released during cell necrosis or tissue damage, acting as an alarmin to alert the immune system [1]. IL33 plays crucial roles in type-2 innate immunity by activating eosinophils, basophils, mast cells, macrophages, and group 2 innate lymphoid cells (ILC2s) via its receptor ST2 [1]. It is involved in various inflammatory, infectious, and autoimmune diseases [3].

In mouse models of spontaneous breast cancer metastasis, targeting IL33 in vivo inhibited lung metastasis and attenuated immune cell recruitment and type 2 immunity, suggesting its role in facilitating breast cancer lung metastasis by modifying the immune microenvironment [2]. In pancreatic cancer mouse models, lack of stromal IL33 led to reprogramming of the tumor microenvironment components like CAFs, myeloid cells, and lymphocytes, along with increased CD8+ T-cell infiltration and reduced tumor growth, indicating its role in promoting pancreatic tumor growth [4].

In conclusion, IL33 is a key cytokine in immune regulation and inflammation, playing important roles in diseases such as allergic diseases, breast cancer, and pancreatic cancer. The use of gene knockout (KO) and conditional knockout (CKO) mouse models has significantly contributed to understanding IL33's functions in these disease conditions, providing insights into potential therapeutic targets.