消化管粘膜免疫の特殊性を応用した腸管免疫機構の統御療法

利用胃肠粘膜免疫的特点进行肠道免疫系统控制治疗

• 批准号: 14021029
• 负责人: 渡辺 守
• 金额: $ 3.84万
• 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 on Priority Areas
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14021029/
• 关键词: IL-7; IL-7レセプター; 腸管免疫; 粘膜リンパ球; 腸管上皮細胞; 骨髄細胞; 慢性大腸炎; 再生医療

本研究は炎症性腸疾患の発症・慢性化機序解明のため、既存の研究とは全く視点を変え、研究代表者が独自に見いだした粘膜局所におけるIL-7を介した新しい免疫調節機構、活性化IL-7レセプター陽性腸管粘膜内リンパ球による炎症惹起機構の考え方に加え、腸管粘膜再生の概念を導入することにより、腸管局所免疫機構の特殊性を利用した新しい治療法の開発を目指す目的で行われた。本年度の研究では腸管上皮細胞が骨髄由来未熟T細胞に発現するIL-7受容体を表出することに注目し、腸管上皮細胞と腸管粘膜内T細胞が同じpathwayを通ることを推定し、ヒト骨髄由来細胞が内胚葉性の腸管上皮細胞に分化しうる可能性を見出した。男性ドナーより同種骨髄移植を受けた女性レシピエントの腸管生検組織を用いて、食道、胃、小腸、大腸においてドナー由来腸管上皮の存在を明らかとした。この結果はこれまで否定されてきた腸管外由来の上皮細胞の存在を示唆する。更に、正常部おけるドナー由来腸管上皮の頻度は低率であったが、上皮再生過程における検討でGVHDの回復期小腸再生上皮では約10-15倍の頻度の上昇を認めた。更に胃潰瘍辺縁の再生上皮では正常腺管に比べ、30-40倍の頻度でドナー由来上皮細胞の存在を認めた。従って、ヒト骨髄由来細胞は急激な上皮傷害を起こした腸管上皮の再生過程をレスキューする役割を果たしていると考えられる。本研究は腸上皮の病的状態、例えば難治性腸疾患における重篤な潰瘍性病変、炎症性病変に対して、骨髄由来細胞による粘膜上皮の再生を目指した治療法の開発につながるものとして注目される。来年度以降、現在解析しつつある腸管上皮の分化を制御する機構を担う分子に対するターゲット療法を開発することは今後、創薬に発展すると考えられる。

In this study, the chronicity mechanism of inflammatory disease syndrome was explained, the existing research instruments were used to complete the study, and the representative of the study was responsible for the introduction of IL-7 by the mucosal bureau. The new immune mechanism, the active IL-7 antibody, the intramucosal inflammation caused by the globular inflammation of the mucous membrane, and the mechanism were investigated. The concept of mucosal regeneration has been introduced into the clinical practice, and the special immunological institutions of the Administration of Administration have made use of the new method of treatment for the purpose of clinical treatment. In this year's study, the origin of the immature T cells, the IL-7 receptors, the intramucosal T cells, the pathway cells, the endodermal cells, the tubular epithelial cells, the endodermal cells, the tubular epithelial cells, the endodermal cells, the tubular epithelial cells, the epithelial cells, the The transplantation of the same kind of bone in men and women after transplantation of the same kind of bone was used in the tissue tissue of the tube, such as the esophagus, stomach, small bone and large bone. The origin of the tube epithelium shows that there is a gap in the tube. The results showed that there was an indication of instigation in the external origin of the epithelial cells. The cause of the disease is that the degree of tubular epithelium is low, the rate of epithelial regeneration is low, and the process of epithelial regeneration is about 10-15 times higher than that of GVHD. The ratio of normal glandular ducts to normal glandular ducts is 30-40 times higher than that of normal glandular ducts in the stomach. The cause of the disease is the acute stimulation of the epithelium and the regeneration of the epithelium of the tube. the process of the regeneration of the tube epithelium. In this study, the symptoms and cases of epithelial disease, chronic diseases, chronic diseases, inflammatory diseases, bone origin, mucosal epithelial regeneration, treatment and treatment were studied in this study. In the coming year, we are now analyzing the management of the differentiation of the epithelium of the tube. The organization is responsible for the molecular management of the disease. In the future, the exhibition will be conducted in the future.

项目成果

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