IL-33 Inhibits Pulmonary Metastasis Of Breast Cancer By Modulating Eosinophils

Interleukin 33(IL-33)is one of the members of the IL-1 cytokine family found in 2005.IL-33 is mainly located in the nucleus,and is expressed in smooth muscle cells,mucosal epidermal cells and vascular endothelial cells.The full length IL-33 acts as a transcription factor.However,IL-33 is cleaved to form a functional cytokine that is released and acts as an alarmin when the cell is damaged or necrotic.IL-33 receptor ST2L,a member of IL-1 receptor family,is mainly expressed on ILC2,Th2 cells,mast cells,eosinophils.Through ligation with ST2L,IL-33 mainly promotes Th2 response and plays a key role in asthma,arthritis and other inflammatory diseases.Previous studies of IL-33 anti-tumor was inconsistent.In IL-33 transgenic mice,activated CD8+T cells and NK cells inhibited tumor growth and metastasis;expression of IL-33 in tumor cell lines significantly inhibited tumor growth in vivo with the rising number of tumor site infiltrating CD8+T cells,NK cells and ILC2s.However,IL-33 could reduce the killing activity of NK cell,leading to its promotion to tumor growth and metastasis.Therefore,there is no definite conclusion of the study between IL-33 and tumor metastasis.On the basis of those,this study hopes to further explore the relationship between IL-33 and tumor metastasis,and to excavate the important function of IL-33 as a cytokine.In this study,BALB/c mice were established for a breast cancer matastasis model through injecting a fluorescently labeled tumor cell line 4T1 from tail veins,then to investigate the effect and mechanism of IL-33 on tumor metastasis.The results showed that systematic administration with human recombinant expression of IL-33 notably inhibited the metastasis of breast cancer in the tumor-bearing mice accompanied by the increasing number of eosinophils in spleen and lung.However,the effect of IL-33 on tumor metastasis was partly reversed when the eosinophils in mice were cleared.Thus,this study suggested that IL-33 may inhibited the metastasis of cancer cells to the lung by inducing ILC2->IL-5->eosinophils pathway.