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Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy

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

abstract 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.
   
keywords 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
   
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 M C, Boivin-Jahns V, Jahns R, Wyss M, Mooser C, Lambrecht B N, Maeder M T, Rickli H, Flatz L, Eriksson U, Geuking M B, McCoy K D, Ludewig B. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science 2019; 366:881-886.
   
type journal paper/review (English)
date of publishing 15-11-2019
journal title Science (366/6467)
ISSN electronic 1095-9203
pages 881-886
PubMed 31727837
DOI 10.1126/science.aav3487
link http://science.sciencemag.org/cgi/content/full/366/6467/881?ijkey=prWyn9fm3ctEE&keytype=ref&siteid=sci
contact Burkhard Ludewig