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IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway

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タイトル: IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway
著者: Sumida, Kentaro 著作を一覧する
Ohno, Yosuke 著作を一覧する
Ohtake, Junya 著作を一覧する
Kaneumi, Shun 著作を一覧する
Kishikawa, Takuto 著作を一覧する
Takahashi, Norihiko 著作を一覧する
Taketomi, Akinobu 著作を一覧する
Kitamura, Hidemitsu 著作を一覧する
発行日: 2015年 9月 1日
出版者: Nature Publishing Group
誌名: Scientific Reports
巻: 5
開始ページ: 13650
出版社 DOI: 10.1038/srep13650
抄録: Myeloid-derived suppressor cells (MDSCs) are immune negative regulators in the tumour microenvironment. Interleukin (IL)-11, a member of IL-6 family cytokines, functions through the unique receptor IL-11 receptor α coupled with the common signal transducer gp130. IL-11-gp130 signalling causes activation of the JAK/STAT3 pathway. IL-11 is highly upregulated in many types of cancers and one of the most important cytokines during tumourigenesis and metastasis. However, the precise effect of IL-11 on differentiation into MDSCs is still unknown. Here, we found that CD11b+CD14+ monocytic MDSCs were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors in the presence of IL-11. IL-11-conditioned PBMCs induced higher expression of immunosuppressive molecules such as arginase-1. A reduction of T-cell proliferation was observed when MDSCs generated in the presence of IL-11 were co-cultured with CD3/CD28-stimulated, autologous T cells of healthy donors. Culture of normal PBMCs with IL-11 led to STAT3 phosphorylation and differentiation into MDSCs via STAT3 activation. We confirmed expressions of both IL-11 and phosphorylated STAT3 in tumour tissues of colorectal cancer patients. These findings suggest that monocytic MDSCs may be induced by IL-11 in the tumour microenvironment. Thus, IL-11-mediated regulation in functional differentiation of MDSCs may serve as a possible target for cancer immunotherapy.
資料タイプ: article
URI: http://hdl.handle.net/2115/67658
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 北村 秀光

 

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