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. 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 now drawn to a close with the departure of G. Pandey, a post-doctoral fellow who left early in the current fiscal year. My collaborators in these experiments at Hopkins continue to work in this area, often using reagents we have supplied or continue to supply. Furthermore, the Oppenheim lab in the NCI, the Caspi lab in the NEI, and other labs outside NIH (e.g. Csernok E et al in Germany, Blood 2006; 107:4440) continue to build on the ideas and experiments that this work has generated. The other 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 Children?s Hospital National Medical Center. Dr. Nina Raben and Dr. Nagaraju are doing imaging studies of the myocytes early in this disease.
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