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微生物肽模拟物可导致致命性炎性心肌病
作者:小柯机器人 发布时间:2019/11/15 12:40:57

瑞士免疫生物学研究所Burkhard Ludewig研究组的最新研究,揭示了微生物来源的肽模拟物可导致致命的炎性心肌病。该项研究成果发表在11月15日出版的《科学》上。

使用自发性自身免疫性心肌炎的小鼠模型,研究人员证明,心肌炎向致死性心脏病的发展过程,取决于与其共生的拟杆菌属肽模拟物,在肠心肌肌球蛋白特异性T辅助细胞(TH)17细胞的印记。抗生素成功预防小鼠致死性疾病,和在人心肌炎患者中观察到的明显拟杆菌特异的CD4 + T细胞和B细胞均表明,共生细菌的模拟肽可促进遗传易感个体炎症性心肌病的发生。通过操纵微生物组,来抑制心脏毒性T细胞产生,将使炎症性心肌病转化为可靶向的疾病。

据了解,心肌炎可通过长期刺激肌球蛋白重链6特异性TH1和TH17细胞发展为炎性心肌病。但是,控制心脏特异性T细胞心脏毒性的机制仍然未知。

附:英文原文

Title: Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Author: Cristina Gil-Cruz, Christian Perez-Shibayama, Angelina De Martin, Francesca Ronchi, Katrien van der Borght, Rebekka Niederer, Lucas Onder, Mechthild Lütge, Mario Novkovic, Veronika Nindl, Gustavo Ramos, Markus Arnoldini, Emma M.C. Slack, Valérie Boivin-Jahns, Roland Jahns, Madeleine Wyss, Catherine Mooser, Bart N. Lambrecht, Micha T. Maeder, Hans Rickli, Lukas Flatz, Urs Eriksson, Markus B. Geuking, Kathy D. McCoy, Burkhard Ludewig

Issue&Volume: 2019/11/15

Abstract: Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6–specific T helper (TH)1 and TH17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin–specific TH17 cells imprinted in the intestine by a commensal Bacteroides species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated Bacteroides-specific CD4+ T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease.

DOI: 10.1126/science.aav3487

Source:https://science.sciencemag.org/content/366/6467/881

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037