Two autoimmune diabetes loci influencing T cell apoptosis control susceptibility to experimental autoimmune myocarditis.
The pathogenesis of immune-mediated myocarditis depends on genetic and environmental factors. To study the genetic mechanisms, we have developed a model of experimental autoimmune myocarditis in the A.SW mouse. Here we provide evidence that loci on murine chromosome 6, and possibly chromosome 1, are involved in regulating susceptibility. Moreover, these loci overlap with loci implicated in other autoimmune diseases including diabetes in the NOD mouse. These two loci also regulate apoptosis in thymocytes as well as peripheral T cells in the NOD mouse, and we report further that A.SW mice demonstrate the same characteristics in apoptosis. These results suggest that common pathogenetic mechanisms involving apoptosis of both thymic and peripheral T cells are shared by multiple autoimmune diseases.
Guler
Mehmet L
ML
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21205, USA.
Ligons
Davinna L
DL
Wang
Yan
Y
Bianco
Michael
M
Broman
Karl W
KW
Rose
Noel R
NR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003520:Cyclophosphamide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009205:Myocarditis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D019655:Quantitative Trait, Heritable; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D005819:Genetic Markers; D003907:Dexamethasone; D003520:Cyclophosphamide