The role of MAdCAM-1 for induction and maintenance of oral tolerance -analysis with animal model of arthritis

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For the purpose of application of Oral torelance to therapy for autoimmune diseases, We studied the physiological roles of the adhesion molecule MAdCAM-1, which expresses specifically at gut-associated lymphoid tissues (GALT), for the induction of oral tolerance. We established several monoclonal antibodies against MAdCAM-1 of rat and estimated as a tool for the coming studies. In the immunohistochemical study using rat at various age, MAdCAM-1 is expressed at skin and thymus in the embryo and neonatal stage. MAdCAM-1 expression is not recognized at skin and thymus in the adult rat, which suggests that MAdCAM-1 might play an important role for the transmigration of lymphocytes at embryo and neonatal stage.When we injected anti-MAdCAM-1 blocking antibody into the rat at the time to induce adjuvant arthritis, the onset of arthritis was made a little earlier. Moreover, the injection of this antibody tended to inhibit the induction of oral tolerance against adjuvant arthritis. Taken together, it is suggested that MAdCAM-1 pathway might Support the induction of oral tolerance. Although it is necessary to confirm the findings in this study, it may be effective for the induction of oral tolerance to strengthen the pathway including MAdCAM-1, for the purpose of application to clinical medicine. It is also necessary to proceed the basic research about the mechanisms of oral tolerance including MAdCAM-1 pathway.