title: IL-33 inhibits the differentiation and immunosuppressive activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.
abstract: Myeloid-derived suppressor cells (MDSCs) contribute to tumor-mediated immune escape by suppressing antitumor immune responses. Interleukin-33 (IL-33) is capable of regulating various immune cell populations; however, the effects of IL-33 on the differentiation of MDSCs have not been well characterized. In this study, we evaluated the effects of IL-33 on MDSCs and found that IL-33 significantly reduced the differentiation of lineage-negative bone marrow progenitor cells into granulocytic MDSCs (G-MDSCs). IL-33-treated MDSCs exhibited diminished immunosuppressive capacity; reduced inhibition on T-cell proliferation and interferon-γ production, and diminished production of reactive oxygen species. However, IL-33 treatment did not affect the frequency of monocytic MDSCs (M-MDSCs) or their production of nitric oxide and expression of arginase-1. Additionally, compared with control MDSCs, IL-33-treated MDSCs had reduced capacity to induce the differentiation or expansion of Treg cells. Moreover, in vivo IL-33 administration significantly decreased MDSCs and G-MDSCs accumulation in the spleen and tumor microenvironment. Also, despite increasing CD4+and CD8+T-cell infiltration, IL-33 administration markedly decreased Treg-cell population in tumor microenvironment. Taken together, our findings indicate that IL-33 reduces the frequency and immunosuppressive activity of G-MDSCs and ultimately the extent of tumor growth.
authors: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors: Hui Xuan
authors: HX
authors: Lim
authors: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors: Seulah
authors: S
authors: Choi
authors: Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors: Daeho
authors: D
authors: Cho
authors: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors: Tae Sung
authors: TS
authors: Kim
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D005260:Female; D007165:Immunosuppression Therapy; D000067596:Interleukin-33 / Q000008:administration & dosage / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects; D059016:Tumor Microenvironment
chemical_list: D000067596:Interleukin-33; D017382:Reactive Oxygen Species