Publication

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

Journal Paper/Review - Nov 15, 2019

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Link to Abstract: http://science.sciencemag.org/cgi/content/abstract/366/6467/881?ijkey=prWyn9fm3ctEE&keytype=ref&siteid=sci

Link to Reprint: http://science.sciencemag.org/cgi/rapidpdf/366/6467/881?ijkey=prWyn9fm3ctEE&keytype=ref&siteid=sci
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Citation
Gil Cruz C, Perez Shibayama C, De Martin A, Ronchi F, Van der Borght K, Niederer R, Onder L, Lütge M, Novkovic M, Nindl V, Ramos G, Arnoldini M, Slack E, Boivin-Jahns V, Jahns R, Wyss M, Mooser C, Lambrecht B, Maeder M, Rickli H, Flatz L, Eriksson U, Geuking M, McCoy K, Ludewig B. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science 2019; 366:881-886.
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Type
Journal Paper/Review (English)
Journal
Science 2019; 366
Publication Date
Nov 15, 2019
Issn Print
Issn Electronic
1095-9203
Pages
881-886
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Brief description/objective

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T)1 and T17 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 T17 cells imprinted in the intestine by a commensal species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated 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.