膠原病合併間質性肺疾患における肺局所リンパ球の免疫制御機構の解明

阐明间质性肺病并发胶原病中局部肺淋巴细胞的免疫调控机制

• 批准号: 22KJ2730
• 负责人: 中澤 真帆
• 金额: $ 2.83万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2023
• 资助国家: 日本
• 起止时间: 2023-03-08 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22KJ2730/
• 关键词: 特発性炎症性筋疾患

間質性肺疾患は関節リウマチや特発性炎症性筋疾患等、自己免疫性疾患に高率に合併し予後不良な病態にもかかわらず、確立された治療法はなく病態は不明である。申請者は以前、膠原病合併間質性肺疾患における肺局所の免疫細胞の表現型を詳細に解析し報告した。その結果からcoinhibitory分子陽性T細胞は抗原特異的に機能し、抗原特異的B細胞の自己反応性抗体産生に関与している可能性が考えられた。そこで膠原病合併間質性肺疾患において、高い間質性肺疾患合併率が報告されている抗Jo-1抗体陽性特発性炎症性筋疾患合併間質性肺疾患に着目し、自己反応性抗原特異的B細胞の特徴の解明を目的とした。本年度は、まず抗Jo-1抗体特発性炎症性筋疾患患者の末梢血中における抗原特異的B細胞の同定を目指した。抗Jo-1抗体の対応抗原はヒスチジルtRNA合成酵素であることが報告されている。そこで、ビオチン化したヒスチジルtRNA合成酵素を作成し、蛍光標識ストレプトアビジンと反応させることで蛍光標識ヒスチジルtRNA合成酵素4量体を作成した。末梢血から末梢血単核細胞を単離し、B細胞を濃縮した検体を用いて、患者末梢血中のヒスチジルtRNA合成酵素結合B細胞の検出を目指した。しかし作成した4量体に非特異的に結合するB細胞を多数検出した。ヒスチジルtRNA合成酵素は約60kDaと比較的大きい分子であり、非特異的結合B細胞の除去が必要と考えられた。またヒスチジルtRNA合成酵素は3つのドメインをもつことが知られており、そのドメインを用いた4量体の作成、比較検討を予定している。

There are some diseases such as idiopathic inflammatory tendons, and self-immune diseases with a high rate of complication, and make sure that the disease status is unknown. Before the applicant, the original disease combined with sexual lung disease, the immune cell type of the lung bureau was analyzed and the report was reported. The results showed that coinhibitory molecular specific T cell antigen specificity, antigen specific B cell antigen specific antibody and the possibility of immune response were tested. Report on the complication rate of idiopathic inflammatory tendon disease, anti-Jo-1 antibody, idiopathic inflammatory tendon disease, idiopathic pulmonary disease, anti-inflammatory tendon disease, anti-inflammatory lung disease, anti-inflammatory lung disease, anti-inflammatory tendon disease, anti-inflammatory ten This year, the B cells of anti-Jo-1 antibody specific inflammatory tendons in the peripheral blood of patients with idiopathic inflammatory tendons disease were the same as those of the patients with specific antigen. Anti-Jo-1 antibodies, antigens, tRNA synthesis enzymes, tRNA synthesis enzymes, antigens, enzymes, enzymes. In this paper, the tRNA synthesis enzyme is made, and the tRNA synthesis enzyme is made by measuring the volume of tRNA synthesis enzyme. The peripheral blood nuclei were isolated from the peripheral blood, the B cells were isolated from the peripheral blood, and the peripheral blood of the patients were detected by the combination of tRNA synthesis enzymes and B cells. Most of the cells are made into a combination of 4-dimensional non-specific cells. The tRNA biosynthesis enzyme was compared with the large molecular weight of 60kDa, and the non-specific combination of B cell was used to remove the necessary enzyme. The tRNA synthesis enzyme was used to measure the activity of the enzyme 3 times higher than that of the control group, which was made of 4-volume measurement.