Immunopathogen Autoimmune Inflammatory Myopathies--polymyositis/dermatomyositis

自身免疫性炎性肌病-多发性肌炎、皮肌炎和相关疾病的免疫病理特征：肌细胞的淋巴细胞性破坏，以及由一组显著的疾病特异性自身抗体区分的体液自身免疫。虽然肌肉细胞的破坏似乎是由淋巴细胞介导的，但自身抗体，特别是那些针对功能相关但结构不同的氨酰-tRNA合成酶家族的抗体，为研究这种疾病提供了一个有用的窗口，并且是该小组多年来研究的重点。对自身抗体、氨酰-tRNA自身抗原结构的这些研究在几年前导致观察到HRS和另一种肌炎特异性自身抗原AsnRS分别通过CCR 5和CCR 3对未成熟树突状细胞（iDC）具有化学引诱活性; LysRS和AspRS缺乏化学引诱活性。我在霍普金斯的这些实验的合作者继续在这一领域工作，经常使用我们提供或继续提供的试剂。该实验室正在积极开展的另一项工作是由肌肉细胞上MHC I类上调引起的肌炎小鼠模型。K. Nagaraju，这个实验室的一个前研究员，他开发了这个模型，他首先搬到了霍普金斯的罗森实验室，现在在儿童医院国家医学中心的霍夫曼实验室。在过去的一年里，我们向几个外部实验室提供了纯化的自身抗原或表达构建体，而没有正式合作我们感兴趣的项目。其他自身抗原的进一步实验，负责趋化因子活性的受体，以及作用机制，以及在本实验室进行的相关生物学研究已经接近尾声。

Immunopathogenetic features characterize the autoimmune inflammatory myopathies - polymyositis, dermatomyositis, and related diseases: lymphocytic destruction of muscle cells, and humoral autoimmunity distinguished by a striking set of disease-specific autoantibodies. Although the muscle cell destruction appears to be mediated by lymphocytes, the autoantibodies, particularly those directed against the family of functionally related but structurally diverse aminoacyl-tRNA synthetases, offer a useful window on the disease and were the focus of much of this group's research for a number of years. These studies of the autoantibodies, of the structure of the aminoacyl-tRNA autoantigens led several years ago to the observation that HRS and another myositis specific autoantigen, AsnRS, have chemoattractant activity for immature dendritic cells (iDC), via CCR5 and CCR3 respectively; that SerRS, an occasional autoantigen in lupus, has chemoattractant activity for CCR3-transfected cells, but not for iDC; and that LysRS and AspRS lacked chemoattractant activity. My collaborators in these experiments at Hopkins continue to work in this area, often using reagents we have supplied or continue to supply. Another line of work emanating from this lab that is being actively pursued is the mouse model of myositis caused by the up-regulation of MHC Class I on muscle cells. K. Nagaraju, A former fellow in this lab who developed this model moved first to the Rosen lab at Hopkins and is now in the Hoffman lab at the Childrens Hospital National Medical Center. In the past year, we have provided purified autoantigens or expression constructs to several outside labs without formal collaboration for projects of interest to us. Further experiments with other autoantigens, with the receptors responsible for the chemokine activity, and the mechanism of action, and associated biological studies carried out in this lab have drawn to a close.