IL-33通过诱生Treg促进小鼠乳腺癌发展的作用及机制

IL-33是一种具有多重生物学效应的细胞因子。申报者前期已报道IL-33通过促进Treg细胞应答或降低IFN-γ分泌等参与免疫相关疾病，但是关于IL-33在肿瘤尤其是乳腺癌中的作用尚不清楚。申报者发现，阻断IL-33可抑制小鼠乳腺癌发展并降低Treg数量，且IL-33与人乳腺癌具有一定相关性。本研究拟使用乳腺癌荷瘤小鼠、ST2基因敲除鼠及IL-33转基因鼠，采取细胞过继输注、抗体阻断等干预措施，使用免疫荧光、免疫印迹、实时定量PCR、ELISA等实验方法，首先研究IL-33在小鼠乳腺癌中的生物学功能；其次明确IL-33通过诱生Treg来促进小鼠乳腺癌发展及机制；最后使用临床样本分析IL-33、Treg与人乳腺癌的相关性，以期与动物实验结论相印证。本项目可为探索临床乳腺癌干预的新策略提供理论依据。

Interleukin-33 (IL-33) is a newly reported cytokine that plays various roles in human diseases and experimental disease models. Our previous studies have reported that IL-33 is involved in immune-correlated diseases by enhancing regulatory T cell (Treg) responses or reducing interferon-γ production, but the role of IL-33 in tumor especially mammary carcinoma remains unclear. We observed that blockade of IL-33 could ameliorate mouse mammary carcinoma progression and decrease the amount of Treg; moreover, for human being, mammary carcinoma is accompanied with significantly higher serum level of IL-33. Our investigation would explore ST2-/- mice, IL-33-transgenic mice and tumor-bearing mice to study the role of IL-33 in mammary carcinoma by using immunofluorescence, western blot, real-time PCR, ELISA et al.; then, to demonstrate the mechanism by which IL-33 accelerates tumor progression through induction of Treg; last, to confirm our conclusion above by analyzing breast tumor tissues and serum from patients with mammary carcinoma. Our program will declare the mechanism that IL-33 could accelerate mammary carcinoma progression by inducing Treg, and may provide more scientific evidences for establishing new therapeutic target for human tumor treatment especially mammary carcinoma.