权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Establishment of a novel therapy of Inflammatory bowel disease by inducible oral tolerance

通过诱导口服耐受建立炎症性肠病新疗法

基本信息

批准号：
13670498
负责人：
KANAI Takanori
金额：
$ 1.92万
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 (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670498/
关键词：
inflammatory bowel disease therapy mucosal immunity oral tolerance commensal bacteria IgA chronic colitis costimulation OX40

项目摘要

For years medical researchers have strived to develop selective immunotherapies that could specifically ameliorate pathogenic immune responses without immunocompromising the patient. Blockade of many known receptors on T cells can inhibit the initiation of immune responses. However, this approach is problematic in that it is not possible to predict the onset of disease in patients. Current immunotherapies are unsatisfactory for sporadic exacerbating-type of diseases such as multiple sclerosis and inflammatory bowel disease (IBD), because they require either long-term treatment or acute treatment with high-dose immunosuppressants. With regard to this issue, the inducible and inflammatory site-specific molecule, inducible co-stimulator (ICOS), may be particularly useful as an ideal targeting molecule for the strategy of treatment of human IBD patients. First, we found significantly increased expression of ICOS on T cells in inflamed colon from both IBD patients and colitic mice, but not in uninflamed mucosa and in periphery. Based on these results, we demonstrated anti-ICOS mAb ameliorated chronic murine experimental colitis when administrated either early or late after induction of colitis. In addition, we are under investigation to establish a bacterium genetically enginneered to secrete soluble costimulatory molecules to inhibit physiological costimulatory pathway for a novel therapy of IBD.

多年来，医学研究人员一直致力于开发选择性免疫疗法，可以特异性地改善致病性免疫反应，而不会损害患者的免疫功能。阻断T细胞上的许多已知受体可以抑制免疫应答的启动。然而，这种方法是有问题的，因为不可能预测患者的疾病发作。目前的免疫疗法对于散发性加重型疾病如多发性硬化症和炎症性肠病（IBD）是不令人满意的，因为它们需要长期治疗或用高剂量免疫抑制剂进行急性治疗。关于这个问题，诱导型和炎症位点特异性分子，诱导型共刺激分子（ICOS），可能是特别有用的，作为一个理想的靶向分子的策略，治疗人类IBD患者。首先，我们发现IBD患者和结肠炎小鼠的炎症结肠中T细胞上ICOS的表达显著增加，但在未炎症粘膜和外周中没有。基于这些结果，我们证明了在诱导结肠炎后早期或晚期给予抗ICOS mAb可改善慢性小鼠实验性结肠炎。此外，我们正在研究建立一种基因工程细菌，分泌可溶性共刺激分子，以抑制生理性共刺激途径，为IBD的新治疗。