title: Transgenic expression of IL-33 activates CD8(+) T cells and NK cells and inhibits tumor growth and metastasis in mice.
abstract: IL-33 is a multifunctional cytokine in immune regulation that activates Th1 cells, Th2 cells, CD8(+) T cells and NK cells. Our study showed that transgenic expression of IL-33 attenuated tumor metastasis in the B16 melanoma and Lewis lung carcinoma (LLC) metastatic models. The percentages and cytotoxicity of CD8(+) T cells and NK cells and their infiltration into the tumor tissues were significantly increased by the transgenic expression of IL-33 in tumor-bearing mice. Treatment with recombinant IL-33 could also increase the cytotoxicity of CD8(+) T cells and NK cells in vitro. In addition, depletion of CD8(+) T cells and NK cells using anti-CD8 or anti-asialo GM1 antibody abolished the pulmonary metastasis inhibition mediated by IL-33. Furthermore, IL-33 stimulated the activation of NF-κB and increased CD69 expression, which is a marker of the activated form of the two cell subsets, in CD8(+) T cells and NK cells. Our results suggest that IL-33 stimulated NF-κB signaling and promoted the proliferation, activation and infiltration of CD8(+) T cells and NK cells, which resulted in the inhibition of pulmonary metastasis in B16 melanoma and LLC mice models.
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, and Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Gao
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.forename: Guiying
authors.initials: G
authors.lastname: Shi
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
authors.forename: Lingying
authors.initials: L
authors.lastname: Wu
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology; D009362:Neoplasm Metastasis / Q000235:genetics
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D016328:NF-kappa B