结肠炎
炎症性肠病
原发性硬化性胆管炎
病态的
FOXP3型
炎症
免疫学
溃疡性结肠炎
免疫系统
医学
生物
病理
疾病
作者
Franziska Mathies,Niklas Steffens,Doerte Kleinschmidt,Friederike Stuhlmann,Francis Huber,Urmi Roy,Thomas Meyer,Marc Luetgehetmann,Mareike von Petersdorff,Oliver Seiz,Johannes Herkel,Christoph Schramm,Richard A. Flavell,Nicola Gagliani,Christian Krebs,Ulf Panzer,Zeinab Abdullah,Till Strowig,Tanja Bedke,Samuel Huber
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2018-12-15
卷期号:201 (12): 3558-3568
被引量:16
标识
DOI:10.4049/jimmunol.1800711
摘要
Inflammatory bowel disease is associated with extraintestinal diseases such as primary sclerosing cholangitis in the liver. Interestingly, it is known that an imbalance between Foxp3+ regulatory T cells (Treg) and Th17 cells is involved in inflammatory bowel disease and also in primary sclerosing cholangitis. To explain these associations, one hypothesis is that intestinal inflammation and barrier defects promote liver disease because of the influx of bacteria and inflammatory cells to the liver. However, whether and how this is linked to the Treg and Th17 cell imbalance is unclear. To address this, we used dextran sodium sulfate (DSS) and T cell transfer colitis mouse models. We analyzed the pathological conditions of the intestine and liver on histological, cellular, and molecular levels. We observed bacterial translocation and an influx of inflammatory cells, in particular Th17 cells, to the liver during colitis. In the DSS colitis model, in which Treg were concomitantly increased in the liver, we did not observe an overt pathological condition of the liver. In contrast, the T cell-mediated colitis model, in which Treg are not abundant, was associated with marked liver inflammation and a pathological condition. Of note, upon depletion of Treg in DEREG mice, DSS colitis promotes accumulation of Th17 cells and a pathological condition of the liver. Finally, we studied immune cell migration using KAEDE mice and found that some of these cells had migrated directly from the inflamed intestine into the liver. Overall, these data indicate that colitis can promote a pathological condition of the liver and highlight an important role of Treg in controlling colitis-associated liver inflammation.
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