Unifying roles for regulatory T cells and inflammation in cancer.
Unifying roles for regulatory T cells and inflammation in cancer.
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DOI：
10.1002/ijc.24923
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发表时间：
2010-04-01
影响因子：
6.4
通讯作者：
Poutahidis, Theofilos
中科院分区：
文献类型：
--
作者：
Erdman, Susan E.;Rao, Varada P.;Olipitz, Werner;Taylor, Christie L.;Jackson, Erin A.;Levkovich, Tatiana;Lee, Chung-Wei;Horwitz, Bruce H.;Fox, James G.;Ge, Zhongming;Poutahidis, Theofilos
在慢性炎症性疾病期间，CD4+调节(Treg)细胞的活动恢复免疫平衡。然而，Treg细胞在炎症相关癌症中的作用是矛盾的。人们普遍认为Treg在癌症中的作用主要是抑制保护性的抗癌反应。然而，我们在这里证明，Treg细胞也可以通过有效地降低胃肠道(GI)引起的炎症来降低全身的癌症风险。建立在“卫生假说”模型的基础上，胃肠道感染导致Treg的变化，从而减少免疫介导的疾病，在这里，我们展示了肠道细菌触发的Treg即使在肠外部位也可能起到抑制癌症的作用。细菌刺激的Treg抑制癌症的能力依赖于IL-10，IL-10用于维持肠道内的免疫动态平衡，并支持保护性抗炎Treg表型。然而，在促炎条件下，Treg可能无法提供抗炎保护，而是有助于T辅助(Th)-17驱动的致癌过程；这种癌症状态可以通过下调炎症来逆转。因此，IL-10和Treg介导的抑制环减弱的卫生个人非常容易受到IL-6和IL-17升高的致癌后果的影响，并表现出更频繁的炎症相关癌症。综上所述，这些数据统一了看似不同的疾病过程，如自身免疫和癌症，并有助于解释癌症中Treg和炎症的悖论。增强Treg的保护性功能可能会促进健康长寿，并显著降低癌症风险。
Activities of CD4+ regulatory (TREG) cells restore immune homeostasis during chronic inflammatory disorders. Roles for TREG cells in inflammation-associated cancers, however, are paradoxical. It is widely believed that TREG function in cancer mainly to suppress protective anticancer responses. However, we demonstrate here that TREG cells also function to reduce cancer risk throughout the body by efficiently downregulating inflammation arising from the gastrointestinal (GI) tract. Building on a “hygiene hypothesis” model in which GI infections lead to changes in TREG that reduce immune-mediated diseases, here we show that gut bacteria-triggered TREG may function to inhibit cancer even in extraintestinal sites. Ability of bacteria-stimulated TREG to suppress cancer depends on interleukin (IL)-10, which serves to maintain immune homeostasis within bowel and support a protective antiinflammatory TREG phenotype. However, under proinflammatory conditions, TREG may fail to provide antiinflammatory protection and instead contribute to a T helper (Th)-17-driven procarcinogenic process; a cancer state that is reversible by downregulation of inflammation. Consequently, hygienic individuals with a weakened IL-10 and TREG-mediated inhibitory loop are highly susceptible to the carcinogenic consequences of elevated IL-6 and IL-17 and show more frequent inflammation-associated cancers. Taken together, these data unify seemingly divergent disease processes such as autoimmunity and cancer and help explain the paradox of TREG and inflammation in cancer. Enhancing protective TREG functions may promote healthful longevity and significantly reduce risk of cancer.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
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50.3
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Wang TC
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通讯作者：
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82.9
作者：
Fox, JG;Beck, P;Nagler-Anderson, C
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Nagler-Anderson, C
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158.5
作者：
Chlebowski, RT;Wactawski-Wende, J;Carleton, R
通讯作者：
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