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Nishina, Takashi; Deguchi, Yutaka; Ohshima, Daisuke; Takeda, Wakami; Ohtsuka, Masato; Shichino, Shigeyuki; Ueha, Satoshi; Yamazaki, Soh; Kawauchi, Mika; Nakamura, Eri; Nishiyama, Chiharu; Kojima, Yuko; Adachi-Akahane, Satomi; Hasegawa, Mizuho; Nakayama, Mizuho; Oshima, Masanobu; Yagita, Hideo; Shibuya, Kazutoshi; Mikami, Tetuo; Inohara, Naohiro; Matsushima, Kouji; Tada, Norihiro; Nakano, Hiroyasu
Nature communications, 04/2021, Volume: 12, Issue: 1Journal Article
Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11 ) cells are not fully understood. To characterize IL-11 cells in vivo, we generate Il11 reporter mice. IL-11 cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11 cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11 fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11 fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.
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