The Mechanism Of IL-33 Inhibiting Breast Cancer Metastasis To Lung

IL-33 is a member of the IL-1 family and as a cell endogenous alarmin,released by damaged or necrotic barrier cells(endothelial and epithelial cells).The signal transduction of IL-33 depends on interaction with the specific receptor ST2L,which mainly expressed in immune cells.IL-33 plays an important role in innate immunity and adoptive immunity,and is involved in regulating the homeostasis and response to environmental stress.IL-33 plays a dual role in different diseases through different immunological mechanisms:paticipating in Th2-related diseases such as allergic asthma and arthritis by stimulating Th2-type immune responses,or playing a protective role in inflammation-related arteriosclerosis and infection-induced tissue damage.The role of IL-33 in tumor research are different:on the one hand by promoting MDSC and other immunosuppressive cell proliferation,promote breast cancer or colon cancer growth and metastasis;on the other hand,using of IL-33 transgenic mice?overexpression of IL-33 in tumor cells or as an immunoadjuvant,the study found that IL-33 can promote CD8~+T,NK cell infiltration,ILC2 proliferation,DC activation and thus inhibit tumor growth and metastasis.Tumor metastasis is the mainly cause of treatment failure and recurrence,and chemotherapy is currently the most widely used to control the postoperative tumor metastasis.Early detection of serum in patients with chemotherapy found that due to cell killing by chemotherapy,resulting in a significant increase in IL-33 expression.To this end,this paper uses breast cancer to transfer the mouse model to explore the role of IL-3 3 in tumor metastasis and possible mechanisms.In this study,we used the high metastatic breast cancer cell line 4T1-luciferase to establish tumor metastasis model by tail vein injection,and to give the recombinant IL-33.It was found that IL-33 could significantly inhibit the lung metastasis of breast cancer.The levels of CD8~+ T,NK,B,ILC2 and eosinophils in the spleen and lung were significantly increased by IL-33,and the expression of IL-5,IFNy and chemokine CCL5 Also significantly increased.With IL-33 specific receptor ST2 gene knockout mice we prove that IL-33 inhibit breast cancer metastasis through IL-33/ST2 signaling pathways which regulate immune response.The use of IL-5 and CD8 antibody to deplete eosinophils and CD8~+ T cells respective in mice could attenuate tumor metastasis to some extent.When eliminating eosinophils and CD8~+ T cells at the same time,the effect of that IL-33 inhibits breast cancer metastasis to the lungs can be significantly reversed.The results showed that IL-33 could inhibit the breast cancer metastasis to lung by promoting synergistic effect of IL-5 which produced by ILC2 and CD8~+ T cell.IL-33 was used as tumor immunotherapy Cytokines provide a theoretical basis.