1] Genentech, South San Francisco, California, USA [2] Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
Mucosal Immunol. 2015 Jul;8(4):720-30. doi: 10.1038/mi.2015.40. Epub 2015 May 6.
Compromised intestinal barrier function is a prominent feature of inflammatory bowel disease (IBD). However, links between intestinal barrier loss and disease extend much further, including documented associations with celiac disease, type I diabetes, rheumatoid arthritis, and multiple sclerosis. Intestinal barrier loss has also been proposed to have a critical role in the pathogenesis of graft-versus-host disease (GVHD), a serious, potentially fatal consequence of hematopoietic stem cell transplantation. Experimental evidence has begun to support this view, as barrier loss and its role in initiating and establishing a pathogenic inflammatory cycle in GVHD is emerging. Here we discuss similarities between IBD and GVHD, mechanisms of intestinal barrier loss in these diseases, and the crosstalk between barrier loss and the immune system, with a special focus on natural killer (NK) cells. Unanswered questions and future research directions on the topic are discussed along with implications for treatment.
肠道屏障功能受损是炎症性肠病 (IBD) 的一个突出特征。然而，肠道屏障丧失与疾病之间的联系远不止于此，包括与乳糜泻、1 型糖尿病、类风湿关节炎和多发性硬化症的明确关联。肠道屏障丧失也被认为在移植物抗宿主病 (GVHD) 的发病机制中起关键作用，GVHD 是造血干细胞移植的一种严重的、潜在致命的后果。实验证据开始支持这一观点，因为在 GVHD 中，屏障丧失及其在引发和建立致病炎症循环中的作用正在显现。在这里，我们讨论了 IBD 和 GVHD 之间的相似性、这些疾病中肠道屏障丧失的机制，以及屏障丧失与免疫系统之间的串扰，特别关注自然杀伤 (NK) 细胞。还讨论了该主题的未解决问题和未来研究方向，以及对治疗的影响。
