| First Author | Gil-Cruz C | Year | 2019 |
| Journal | Science | Volume | 366 |
| Issue | 6467 | Pages | 881-886 |
| PubMed ID | 31727837 | Mgi Jnum | J:323385 |
| Mgi Id | MGI:6377653 | Doi | 10.1126/science.aav3487 |
| Citation | Gil-Cruz C, et al. (2019) Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science 366(6467):881-886 |
| abstractText | 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. |
