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

MAdCAM-1 在诱导和维持口服耐受中的作用 - 关节炎动物模型分析

基本信息

批准号：
11557037
负责人：
MIYASAKA Nobuyuki
金额：
$ 8.64万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

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.

为了将口服耐受性应用于自身免疫性疾病的治疗，我们研究了粘附分子MAdCAM-1在诱导口服耐受性中的生理作用，该分子在肠相关淋巴组织（GALT）中特异性表达。我们建立了几种针对大鼠MAdCAM-1的单克隆抗体，估计可作为今后研究的工具。在不同年龄大鼠的免疫组织化学研究中，MAdCAM-1在胚胎期和新生儿期的皮肤和胸腺中表达。成年大鼠的皮肤和胸腺不识别MAdCAM-1的表达，这表明MAdCAM-1可能在胚胎和新生儿阶段淋巴细胞的转运中起重要作用。当我们在大鼠体内注射抗madcam -1阻断抗体诱导佐剂性关节炎时，关节炎的发病时间提前了一点。此外，注射该抗体倾向于抑制对佐剂关节炎的口服耐受诱导。综上所述，我们认为MAdCAM-1通路可能支持口服耐受的诱导。虽然本研究的发现还需要进一步的证实，但加强包括MAdCAM-1在内的通路可能对诱导口服耐受有效，从而应用于临床医学。对包括MAdCAM-1通路在内的口服耐受机制进行基础研究也是必要的。