IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.
IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.
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作者：
慢性黏膜炎症和组织损伤使患者易患结直肠癌（CRC）。这种关联可以用这样一种假说解释：对伤口愈合起重要作用的相同因素和途径也会促进肿瘤发生。一种组织损伤传感器应诱导这些因素以促进组织修复，并调节它们的作用以防止癌症发生。白细胞介素 - 22（IL - 22）是白细胞介素 - 10超家族的一种细胞因子，对结肠上皮细胞修复起重要作用，并且在炎症性肠病（IBD）患者的血液和肠道中含量增加。这种细胞因子可被可溶性白细胞介素 - 22受体（即白细胞介素 - 22结合蛋白，IL - 22BP，IL - 22RA2）中和，然而内源性白细胞介素 - 22BP在体内的重要性以及调节该受体的途径尚不清楚。我们在此描述白细胞介素 - 22BP在控制结肠肿瘤发生和上皮细胞增殖方面起着至关重要的作用。在稳定状态下，白细胞介素 - 22BP由结肠中的树突状细胞（DC）高度表达。通过NLRP3或NLRP6炎症小体对肠道组织损伤的感知导致白细胞介素 - 22BP以白细胞介素 - 18依赖的方式下调，从而增加白细胞介素 - 22/白细胞介素 - 22BP的比率。在肠道组织损伤过程中被诱导产生的白细胞介素 - 22在损伤高峰期发挥保护作用，但如果在恢复阶段不受控制则会促进肿瘤发展。
因此，白细胞介素 - 22 - 白细胞介素 - 22BP轴对结肠的肠道组织修复和肿瘤发生起着关键的调节作用。
Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer (CRC). This association could be explained by the hypothesis that the same factors and pathways important for wound healing also promote tumorigenesis. A sensor of tissue damage should induce these factors to promote tissue repair and regulate their action to prevent development of cancer. IL-22, a cytokine of the IL-10 superfamily, plays an important role for colonic epithelial cell repair, and is increased in the blood and intestine of IBD patients. This cytokine can be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP, IL-22RA2), however the significance of endogenous IL-22BP in vivo and the pathways that regulate this receptor are unknown. We describe herein that IL-22BP plays a crucial role in controlling tumorigenesis and epithelial cell proliferation in the colon. IL-22BP is highly expressed by dendritic cells (DC) in the colon in steady state conditions. Sensing of intestinal tissue damage via the NLRP3 or NLRP6 inflammasomes led to an IL-18-dependent down regulation of IL-22BP, thereby increasing the ratio of IL-22/IL-22BP. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumor development if uncontrolled during the recovery phase. Thus the IL-22-IL-22BP axis critically regulates intestinal tissue repair and tumorigenesis in the colon.
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DOI：
10.1084/jem.20082683
发表时间：
2009-07-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pickert G;Neufert C;Leppkes M;Zheng Y;Wittkopf N;Warntjen M;Lehr HA;Hirth S;Weigmann B;Wirtz S;Ouyang W;Neurath MF;Becker C
通讯作者：
Becker C
影响因子：
15.9
作者：
Sugimoto, Ken;Ogawa, Atsuhiro;Mizoguchi, Atsushi
通讯作者：
Mizoguchi, Atsushi
影响因子：
30.5
作者：
Duhen, Thomas;Geiger, Rebekka;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
32.4
作者：
Sutterwala, FS;Ogura, Y;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.4
作者：
Kotenko, SV;Izotova, LS;Pestka, S
通讯作者：
Pestka, S