TY - JOUR
T1 - The role of Jo-1 in the immunopathogenesis of polymyositis
T2 - current hypotheses.
AU - Ascherman, Dana P.
PY - 2003/12
Y1 - 2003/12
N2 - Polymyositis represents an autoimmune disease in which T cells mediate destruction of muscle cells. Although the precise trigger(s) for this process remain unknown, distinct clinical subsets exist that are characterized by antibodies directed against specific nuclear and cytoplasmic antigens including Jo-1 (histidyl-transfer RNA synthetase). Coupled with a range of genetic and histomorphologic data, the stereotypical serologic response suggests that antigen-specific T cells directed against Jo-1 can promote T cell-mediated cytolysis of muscle cells as well as anti-Jo-1 antibody formation in selected patients with polymyositis. Beyond a previously developed animal model that has demonstrated the capacity of Jo-1 to promote humoral and cell-mediated immune responses leading to myositis, recent studies have revealed the existence of Jo-1-specific T cells in the peripheral blood of patients with Jo-1 antibody-positive polymyositis. Even more striking, investigators have discovered that Jo-1 can serve as a chemokine for immature dendritic cells and T lymphocytes. Collectively, these findings suggest a mechanism by which Jo-1 can bridge the innate and adaptive immune responses, leading to the breakdown of tolerance and autoimmune destruction of muscle.
AB - Polymyositis represents an autoimmune disease in which T cells mediate destruction of muscle cells. Although the precise trigger(s) for this process remain unknown, distinct clinical subsets exist that are characterized by antibodies directed against specific nuclear and cytoplasmic antigens including Jo-1 (histidyl-transfer RNA synthetase). Coupled with a range of genetic and histomorphologic data, the stereotypical serologic response suggests that antigen-specific T cells directed against Jo-1 can promote T cell-mediated cytolysis of muscle cells as well as anti-Jo-1 antibody formation in selected patients with polymyositis. Beyond a previously developed animal model that has demonstrated the capacity of Jo-1 to promote humoral and cell-mediated immune responses leading to myositis, recent studies have revealed the existence of Jo-1-specific T cells in the peripheral blood of patients with Jo-1 antibody-positive polymyositis. Even more striking, investigators have discovered that Jo-1 can serve as a chemokine for immature dendritic cells and T lymphocytes. Collectively, these findings suggest a mechanism by which Jo-1 can bridge the innate and adaptive immune responses, leading to the breakdown of tolerance and autoimmune destruction of muscle.
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U2 - 10.1007/s11926-003-0052-2
DO - 10.1007/s11926-003-0052-2
M3 - Review article
C2 - 14609486
AN - SCOPUS:1542645062
VL - 5
SP - 425
EP - 430
JO - Current Rheumatology Reports
JF - Current Rheumatology Reports
SN - 1523-3774
IS - 6
ER -