Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.
Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.
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DOI：
10.1371/journal.pone.0100217
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wick MJ
中科院分区：
文献类型：
--
作者：
Wenzel UA;Magnusson MK;Rydström A;Jonstrand C;Hengst J;Johansson ME;Velcich A;Öhman L;Strid H;Sjövall H;Hansson GC;Wick MJ
结肠黏液层通过限制肠道细菌与粘膜免疫系统之间的接触，在肠道内稳态中起着关键作用。在动物模型中，有缺陷的粘液屏障允许细菌与肠上皮接触并导致自发性结肠炎。有缺陷的粘液屏障也是活动性溃疡性结肠炎（UC）的一个关键特征。在缺乏结肠粘液屏障的小鼠中，由于肠道细菌破坏而导致的免疫室改变尚未被表征并与活动性UC相关。在Muc2 - / -小鼠中，由于缺乏结肠粘液屏障，肠道细菌破坏导致免疫室的改变，并将这些发现与活动性UC联系起来。使用荧光显微镜和qPCR检测Muc2−/−小鼠和活动性UC患者结肠活检中细菌与结肠上皮的接触和对结肠组织的渗透。用流式细胞术定量测定Muc2−/−小鼠和UC患者活检组织结肠中的中性粒细胞、淋巴细胞、CD103+树突状细胞亚群和巨噬细胞。炎症性UC患者和Muc2−/−小鼠结肠上皮接触细菌。细菌rRNA存在于人类和Muc2−/−小鼠的结肠粘膜以及小鼠的引流淋巴结中。发炎的Muc2−/−小鼠和UC患者结肠中性粒细胞、T细胞和巨噬细胞升高，而小鼠和人类发炎的结肠中CD103+ dc的频率降低。Muc2−/−小鼠和UC患者结肠免疫细胞室的相似特征支持该模型在了解自发性结肠炎早期阶段的有效性，并将为治疗UC的新策略提供见解。
The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC. To characterize alterations in the immune compartment due to intestinal bacterial breach in Muc2−/− mice, which lack the colon mucus barrier, and correlate the findings to active UC. Bacterial contact with colon epithelium and penetration into colon tissue was examined in Muc2−/− mice and colon biopsies from patients with active UC using fluorescence microscopy and qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in colon from Muc2−/− mice and biopsies from UC patients were quantitated by flow cytometry. Inflamed UC patients and Muc2−/− mice had bacteria in contact with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans and Muc2−/− mice and in the draining lymph nodes of mice. Inflamed Muc2−/− mice and UC patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ DCs was present in the inflamed colon of both mice and humans. The parallel features of the colon immune cell compartment in Muc2−/− mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC.
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影响因子：
3.7
作者：
Beitnes, A. -C. R.;Raki, M.;Jahnsen, F. L.
通讯作者：
Jahnsen, F. L.
影响因子：
24.5
作者：
Iliev, I. D.;Spadoni, I.;Rescigno, M.
通讯作者：
Rescigno, M.
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Lee, James C.;Lees, Charles W.;Prescott, Natalie J.;Anderson, Carl A.;Phillips, Anne;Wesley, Emma;Parnell, Kirstie;Zhang, Hu;Drummond, Hazel;Nimmo, Elaine R.;Massey, Dunecan;Blaszczyk, Kasia;Elliott, Timothy;Cotterill, Lynn;Dallal, Helen;Lobo, Alan J.;Mowat, Craig;Sanderson, Jeremy D.;Jewell, Derek P.;Newman, William G.;Edwards, Cathryn;Ahmad, Tariq;Mansfield, John C.;Satsangi, Jack;Parkes, Miles;Mathew, Christopher G.;Donnelly, Peter;Peltonen, Leena;Blackwell, Jenefer M.;Bramon, Elvira;Brown, Matthew A.;Casas, Juan P.;Corvin, Aiden;Craddock, Nicholas;Deloukas, Panos;Duncanson, Audrey;Jankowski, Janusz;Markus, Hugh S.;McCarthy, Mark I.;Palmer, Colin N. A.;Plomin, Robert;Rautanen, Anna;Sawcer, Stephen J.;Samani, Nilesh;Trembath, Richard C.;Viswanathan, Ananth C.;Wood, Nicholas;Spencer, Chris C. A.;Bellenguez, Celine;Davison, Daniel;Freeman, Colin;Strange, Amy;Langford, Cordelia;Hunt, Sarah E.;Edkins, Sarah;Gwilliam, Rhian;Blackburn, Hannah;Bumpstead, Suzannah J.;Dronov, Serge;Gillman, Matthew;Gray, Emma;Hammond, Naomi;Jayakumar, Alagurevathi;McCann, Owen T.;Liddle, Jennifer;Perez, Marc L.;Potter, Simon C.;Ravindrarajah, Radhi;Ricketts, Michelle;Waller, Matthew;Weston, Paul;Widaa, Sara;Whittaker, Pamela;Attwood, Antony P.;Stephens, Jonathan;Sambrook, Jennifer;Ouwehand, Willem H.;McArdle, Wendy L.;Ring, Susan M.;Strachan, David P.
通讯作者：
Strachan, David P.
影响因子：
64.8
作者：
Khor, Bernard;Gardet, Agnes;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.
影响因子：
8
作者：
Cerovic, V.;Houston, S. A.;Milling, S. W. F.
通讯作者：
Milling, S. W. F.