Characterization of Interleukin 11-producing fibroblasts that constitute a niche for tumor development [Agilent]

Interleukin (IL)-11 belongs to a member of the IL-6 family of cytokines and is involved in a variety of cellular responses. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells rapidly appeared in the colon of mice after dextran sulfate sodium treatment. IL-11+ cells expressed fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11+ cells also appeared in the colon of three murine tumor models and human colorectal cancers. Deletion of Il11ra1 or Il11 attenuated the development of colitis-associated colorectal cancers in mice. IL-11 induced STAT3 phosphorylation in colonic fibroblasts, and injection of IL-11 receptor agonist upregulated many genes that were enriched in IL-11+ cells. Together, tumor cells induced IL-11+ fibroblasts, and a feed-forward loop between IL-11 and IL-11+ fibroblasts might constitute a niche for promoting tumor development. To identify target genes by IL-11 in the colon, we intravenously injected 10 mg of the IL-11 receptor agonist, NT-3N into wild-type C57BL/B6 mice (n=2-3 mice per each time point). Then mice were sacrificed, and the colon was removed at 3 hours after injection.