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

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Title: IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway
Authors: Sumida, Kentaro Browse this author
Ohno, Yosuke Browse this author
Ohtake, Junya Browse this author
Kaneumi, Shun Browse this author
Kishikawa, Takuto Browse this author
Takahashi, Norihiko Browse this author
Taketomi, Akinobu Browse this author →KAKEN DB
Kitamura, Hidemitsu Browse this author →KAKEN DB
Issue Date: 1-Sep-2015
Publisher: Nature Publishing Group
Journal Title: Scientific Reports
Volume: 5
Start Page: 13650
Publisher DOI: 10.1038/srep13650
Abstract: 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.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 北村 秀光

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