Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis.
Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis.
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DOI：
10.1038/ncomms7956
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发表时间：
2015-04-24
影响因子：
16.6
通讯作者：
Zhang, Huang-Ge
中科院分区：
文献类型：
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作者：
Deng, Zhongbin;Mu, Jingyao;Tseng, Michael;Wattenberg, Binks;Zhuang, Xiaoying;Egilmez, Nejat K.;Wang, Qilong;Zhang, Lifeng;Norris, James;Guo, Haixun;Yan, Jun;Haribabu, Bodduluri;Miller, Donald;Zhang, Huang-Ge
肠道相关炎症在结肠癌的发展中起着至关重要的作用。在这里，我们确定了一种新的病原体-宿主相互作用，促进肠道炎症和结肠癌的发展。我们发现，肠道致病细菌分泌颗粒(ET-BSP)刺激肠上皮细胞产生IDEN(肠粘膜衍生外体样纳米颗粒)，其中含有高水平的鞘氨醇-1-磷酸、CCL20和前列腺素E2(PGE2)。CCL20和PGE2分别是Th17细胞募集和增殖所必需的，这些过程也涉及MyD88介导的途径。IDEN通过影响Th17细胞在肠道的募集和增殖，促进结肠癌的发生。我们证明了包含在IDEN中的鞘氨醇-1-磷酸在自发性和移植性结肠癌小鼠模型中对肿瘤生长的生物学效应。这些发现为宿主-微生物关系如何由细菌和宿主细胞分泌的颗粒所调节提供了更深层次的见解。
Gut-associated inflammation plays a crucial role in the progression of colon cancer. Here, we identify a novel pathogen-host interaction that promotes gut inflammation and the development of colon cancer. We find that enteropathogenic bacteria-secreted particles (ET-BSPs) stimulate intestinal epithelium to produce IDENs (intestinal mucosa-derived exosome-like nanoparticles) containing elevated levels of sphingosine-1-phosphate, CCL20 and prostaglandin E2 (PGE2). CCL20 and PGE2 are required for the recruitment and proliferation, respectively, of Th17 cells, and these processes also involve the MyD88-mediated pathway. By influencing the recruitment and proliferation of Th17 cells in the intestine, IDENs promote colon cancer. We demonstrate the biological effect of sphingosine-1-phosphate contained in IDENs on tumor growth in spontaneous and transplanted colon cancer mouse models. These findings provide deeper insights into how host-microbe relationships are mediated by particles secreted from both bacterial and host cells.
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DOI：
10.4049/jimmunol.1203170
发表时间：
2013-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Deng ZB;Zhuang X;Ju S;Xiang X;Mu J;Liu Y;Jiang H;Zhang L;Mobley J;McClain C;Feng W;Grizzle W;Yan J;Miller D;Kronenberg M;Zhang HG
通讯作者：
Zhang HG
影响因子：
64.8
作者：
Esplugues, Enric;Huber, Samuel;Gagliani, Nicola;Hauser, Anja E.;Town, Terrence;Wan, Yisong Y.;O'Connor, William, Jr.;Rongvaux, Anthony;Van Rooijen, Nico;Haberman, Ann M.;Iwakura, Yoichiro;Kuchroo, Vijay K.;Kolls, Jay K.;Bluestone, Jeffrey A.;Herold, Kevan C.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
20.3
作者：
Chizzolini, Carlo;Chicheportiche, Rachel;Dayer, Jean-Michel
通讯作者：
Dayer, Jean-Michel
影响因子：
64.8
作者：
Grivennikov, Sergei I.;Wang, Kepeng;Mucida, Daniel;Stewart, C. Andrew;Schnabl, Bernd;Jauch, Dominik;Taniguchi, Koji;Yu, Guann-Yi;Oesterreicher, Christoph H.;Hung, Kenneth E.;Datz, Christian;Feng, Ying;Fearon, Eric R.;Oukka, Mohamed;Tessarollo, Lino;Coppola, Vincenzo;Yarovinsky, Felix;Cheroutre, Hilde;Eckmann, Lars;Trinchieri, Giorgio;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
30.5
作者：
Lee, Jacob S.;Cella, Marina;McDonald, Keely G.;Garlanda, Cecilia;Kennedy, Gregory D.;Nukaya, Manabu;Mantovani, Alberto;Kopan, Raphael;Bradfield, Christopher A.;Newberry, Rodney D.;Colonna, Marco
通讯作者：
Colonna, Marco