Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model.
Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model.
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DOI：
10.1084/jem.20122308
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发表时间：
2013-05-06
期刊：
影响因子：
--
通讯作者：
Powrie F
中科院分区：
文献类型：
--
作者：
Kirchberger S;Royston DJ;Boulard O;Thornton E;Franchini F;Szabady RL;Harrison O;Powrie F
中和结肠先天淋巴细胞产生的 IL-22 可通过减少 Stat3 的激活来减少上皮细胞的增殖，从而减少细菌诱导的结肠癌的发育不良。炎症性肠病（IBD）患者患结肠癌的风险增加。然而，人们对介导肠道炎症向癌症转变的免疫细胞和细胞因子知之甚少。我们发现，细菌诱导的结肠癌伴随着 IL-17+IL-22+ 结肠先天淋巴细胞 (cILC) 的差异积累，这些细胞在表型上与 LTi 和 NK-22 细胞不同，并且在患有发育不良炎症的小鼠中，它们的消耗阻止了侵袭性结肠癌的发展。对不同 17 型细胞因子功能作用的分析表明，虽然 IL-17 的阻断可抑制肠道炎症的某些参数，但要减少不典型增生和结直肠癌 (CRC)，需要中和 IL-22，这表明 IL-22 在该模型中维持癌症方面具有独特的作用。机制分析表明，IL-22选择性作用于上皮细胞，诱导Stat3磷酸化和增殖。重要的是，我们可以检测人类结直肠癌中的 IL-22+CD3+ 和 IL-22+CD3− 细胞。我们的结果描述了 IL-22 在结肠中的新活性，作为 CRC 持续存在所需的炎症级联的非冗余介质，强调了 IL-22 轴作为结肠癌的新治疗靶点。
Neutralization of IL-22 production from colonic innate lymphoid cells reduces dysplasia in bacterial-induced colon cancer by reducing proliferation of epithelial cells via reduced activation of Stat3. Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17+IL-22+ colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. Analysis of the functional role of distinct Type 17 cytokines shows that although blockade of IL-17 inhibits some parameters of intestinal inflammation, reduction in dysplasia and colorectal cancer (CRC) requires neutralization of IL-22 indicating a unique role for IL-22 in the maintenance of cancer in this model. Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. Importantly, we could detect IL-22+CD3+ and IL-22+CD3− cells in human CRC. Our results describe a new activity of IL-22 in the colon as a nonredundant mediator of the inflammatory cascade required for perpetuation of CRC, highlighting the IL-22 axis as a novel therapeutic target in colon cancer.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
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Yu H
影响因子：
32.4
作者：
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通讯作者：
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