Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies
Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies
复制标题
DOI：
10.1073/pnas.97.16.9209
复制
发表时间：
2000-08-01
影响因子：
11.1
通讯作者：
Plotz, P
中科院分区：
文献类型：
--
作者：
Nagaraju, K;Raben, N;Plotz, P
在人类炎症性肌病（多发性肌炎和皮肌炎）中，早期广泛出现的MHC I类在肌细胞表面和某些肌炎特异性自身抗体的出现是显着的特点。我们已经使用了一个可控的肌肉特异性启动子系统，以上调MHC I类在年轻小鼠的骨骼肌。这些小鼠的临床、生化、组织学和免疫学特征与人类肌炎非常相似。这种疾病是炎症性的，局限于骨骼肌，自我维持，在女性中更严重，并且通常伴有自身抗体，包括在一些小鼠中，组氨酰-tRNA合成酶的自身抗体，这是在自发性人类疾病中发现的最常见的特异性，抗Jo-1。这个模型表明，自身免疫性疾病可能会展开在一个高度特定的模式作为一个明显的非特异性事件的结果-持续上调的MHC I类在组织和特异性的自身抗体来源于刺激的特异性，但从上下文，位置，并可能持续时间的刺激。该模型进一步表明，作为自身免疫性疾病发展的事件的假定顺序需要重新考虑。
In the human inflammatory myopathies (polymyositis and dermatomyositis), the early, widespread appearance of MHC class I on the surface of muscle cells and the occurrence of certain myositis-specific autoantibodies are striking features. We have used a controllable muscle-specific promoter system to up-regulate MHC class I in the skeletal muscles of young mice. These mice develop clinical, biochemical, histological, and immunological features very similar to human myositis. The disease is inflammatory, limited to skeletal muscles, self-sustaining, more severe in females, and often accompanied by autoantibodies, including, in some mice, autoantibodies to histidyl-tRNA synthetase, the most common specificity found in the spontaneous human disease, anti-Jo-1. This model suggests that an autoimmune disease may unfold in a highly specific pattern as the consequence of an apparently nonspecific event-the sustained up-regulation of MHC class I in a tissue-and that the specificity of the autoantibodies derives not from the specificity of the stimulus, but from the context, location, and probably the duration of the stimulus. This model further suggests that the presumed order of events as an autoimmune disease develops needs to be reconsidered.