[Relationship between osteopontin expression and autoimmune disease--analysis of osteopontin expressed in transgenic...

Osteopontin (OPN) has an adhesive recognition sequence such as Arg-Gly-Asp (RGD) tripeptide and is known to be secreted by activated T cells. The concentration of serum OPN protein is elevated in autoimmune-prone MRL-lpr mice as well as SLE patients. Previously it was shown that CD4-CD8- double-negative (DN) T lymphocytes, a major T cell population in MRL-lpr mice, expressed OPN mRNA. Moreover, OPN induced the polyclonal activation of B cells, resulting in the augmented production of immunoglobulin. To analyze the role of OPN in immune system and in autoimmune diseases specifically, we have generated transgenic mice which express OPN. In the transgenic mice, B1 cell population in peritoneal cavity was markedly increased and titer of IgM and IgG3 antibodies in the serum was considerably higher than that in wild type. Most importantly, the titer of IgM anti-double-stranded and single-stranded DNA was significantly elevated in the transgenic mice. These results strongly suggest that OPN may have an important role in propagation and differentiation of B1 cells and production of autoantibodies.