Guler Mehmet L, Ligons Davinna L, Wang Yan, Bianco Michael, Broman Karl W, Rose Noel R
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21205, USA.
J Immunol. 2005 Feb 15;174(4):2167-73. doi: 10.4049/jimmunol.174.4.2167.
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.
免疫介导性心肌炎的发病机制取决于遗传和环境因素。为了研究遗传机制，我们在A.SW小鼠中建立了实验性自身免疫性心肌炎模型。在此，我们提供证据表明，小鼠6号染色体上的基因座，可能还有1号染色体上的基因座，参与调节易感性。此外，这些基因座与其他自身免疫性疾病相关的基因座重叠，包括非肥胖糖尿病（NOD）小鼠的糖尿病。这两个基因座还调节NOD小鼠胸腺细胞以及外周T细胞的凋亡，并且我们进一步报告，A.SW小鼠在凋亡方面表现出相同的特征。这些结果表明，涉及胸腺和外周T细胞凋亡的共同发病机制在多种自身免疫性疾病中是共有的。
