| 概要： |
Antibodies against the ubiquitously expressed protein
glucose-6-phosphate-isomerase (GPI)induce arthritis in the K/BxN mouse model. When serum containing these autoantibodies is injected healthy mice, the innate immune system is mobilized and arthritis soon develops. This system has revealed novel mechanisms for imposing tissue specificity on autoimmune/inflammatory processes. The first has to do with restraints on activation of the alternative pathway of complement: GPI is found constitutively aligned on the acellular surface where the cartilage meets the articular cavity; being acellular, and thereby lacking cellular complement inhibitors, such a surface can permit complement activation that is effectively extinguished at other sites. The second mechanism is related to the vasculature: immune complexes, even those entailing non-joint antigens, promote vascular leakage specifically at the joints, predisposing them to leukocytic infiltration. Thirdly, there may also be a role for regulatory T cells in containing inflammation to particular tissues. Thus, a tissue-specific disease need not issue from reaction to a tissue-specific antigen, but may instead reflect structural/physiological particularities of the target site.
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