Gil-Cruz, Cristina; Perez-Shibayama, Christian; De Martin, Angelina; Ronchi, Francesca; van der Borght, Katrien; Niederer, Rebekka; Onder, Lucas; Lütge, Mechthild; Novkovic, Mario; Nindl, Veronika; Ramos, Gustavo; Arnoldini, Markus; Slack, Emma M C; Boivin-Jahns, Valérie; Jahns, Roland; Wyss, Madeleine; Mooser, Catherine; Lambrecht, Bart N; Maeder, Micha T; Rickli, Hans; ... (2019). Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science, 366(6467), pp. 881-886. American Association for the Advancement of Science 10.1126/science.aav3487
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie |
UniBE Contributor: |
Ronchi, Francesca, Mooser, Catherine |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0036-8075 |
Publisher: |
American Association for the Advancement of Science |
Language: |
English |
Submitter: |
Lara Schindler |
Date Deposited: |
27 Jan 2020 09:51 |
Last Modified: |
05 Dec 2022 15:35 |
Publisher DOI: |
10.1126/science.aav3487 |
PubMed ID: |
31727837 |
BORIS DOI: |
10.7892/boris.138190 |
URI: |
https://boris.unibe.ch/id/eprint/138190 |
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