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肠道微生物共同作用加剧脊髓炎症
2020-08-27 14:47

日本综合医学科学中心Hiroshi Ohno课题组取得一项新突破。他们的研究发现肠道微生物共同作用加剧脊髓炎症。2020年8月26日,《自然》杂志发表了这项成果。

他们显示了来自肠道微生物的两个截然不同的信号,协调激活了小肠中对髓磷脂少突胶质细胞糖蛋白(MOG)特异反应的自身反应性T细胞。在小鼠中,诱发实验性自身免疫性脑脊髓炎后,在小肠中观察到MOG特异性CD4 + T细胞。使用小肠微生物单一的无菌小鼠进行的实验表明,紫锥菊科中新分离出的菌株与佐剂的作用相似,可增强T辅助17细胞的应答。

对小肠内容物的基因枪法测序揭示了路透氏乳杆菌菌株具有类似MOG的肽。与这两种毒株共定殖的小鼠表现出实验性自身免疫性脑脊髓炎的症状,其症状要比无菌或单一菌种的小鼠严重。这些数据表明,在多发性硬化症的致病性中应考虑到由这些微生物的存在所产生的协同作用,对这些微生物的进一步研究可能导致该疾病的预防策略。

据介绍,越来越多的证据表明,肠道微生物在自身免疫疾病(包括多发性硬化症)中具有致病作用。实验性自身免疫性脑脊髓炎(一种多发性硬化症的动物模型)以及人体研究均已将肠道微生物与多发性硬化症的发生或严重程度联系在一起。然而,尚不清楚肠道微生物如何作用于肠外组织,如脊髓炎症。

附:英文原文

Title: Gut microorganisms act together to exacerbate inflammation in spinal cords

Author: Eiji Miyauchi, Seok-Won Kim, Wataru Suda, Masami Kawasumi, Satoshi Onawa, Naoko Taguchi-Atarashi, Hidetoshi Morita, Todd D. Taylor, Masahira Hattori, Hiroshi Ohno

Issue&Volume: 2020-08-26

Abstract: Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis1. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)2,3, as well as human studies4,5,6, have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.

DOI: 10.1038/s41586-020-2634-9

Source: https://www.nature.com/articles/s41586-020-2634-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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