Analyses of Regulatory Mechanisms in Oral Immune Responses and Development of a New Immunotherapy Targeting Dendritic Cells

口腔免疫反应调节机制分析及针对树突状细胞的新型免疫疗法的开发

• 批准号: 20249075
• 负责人: AZUMA Miyuki
• 金额: $ 31.03万
• 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 (A)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20249075/
• 关键词: 免疫; 感染; 炎症; 口腔粘膜; 樹状細胞; 歯髄; 免疫療法; RNA干渉

Migrating dendritic cells (DC) from oral mucosa into regional lymph nodes were divided into four subsets similar to cutaneous migrating DCs. CD207-CD11c^<hi> F1-DCs that migrated quickly, expressed the highest levels of co-signal molecules, whereas CD207+CD11c^<int/lo> F3-DCs that migrated at the later time point were further divided into both CD103+CD207+ submucosal DCs and CD103- Langerhans cells (LCs) and the latter expressed the lowest co-signal molecules, suggest tolerogenic properties. We demonstrated that using mouse skin allergic models, silencing of CD86 co-signal molecule in skin DCs by RNA interference efficiently inhibited both early innate immune responses at the local site and adaptive immune responses in the secondary lymphoid tissues.

从口腔粘膜迁移到区域淋巴结的树突状细胞（DC）分为四个亚群，类似于皮肤迁移DC。快速迁移的CD 207-CD 11 c ^<hi>F1-DCs表达最高水平的共信号分子，而在较晚时间点迁移的CD 207 + CD 11 c ^F3-DCs进一步分为CD 103 + CD 207+粘膜下DCs和CD 103- Langerhans细胞（LC），后者表达最低水平的共信号分子，表明致耐受性特性。我们证明，使用小鼠皮肤过敏模型，通过RNA干扰沉默皮肤DC中的CD 86辅助信号分子有效地抑制了局部位点的早期先天免疫应答和次级淋巴组织中的适应性免疫应答。

项目成果

The Glucocorticoid-induced TNFR-related protein (GITR)-GITR ligand pathway acts as a mediator of cutaneous dendritic cell migration and promotes T-cell mediated acquired immunity.

糖皮质激素诱导的 TNFR 相关蛋白 (GITR)-GITR 配体途径充当皮肤树突状细胞迁移的介质，并促进 T 细胞介导的获得性免疫。

• 发表时间: 2009
• 期刊: J Immunol 182
• 作者: Kamimura Y;Iwai H;Piao J;Hashiguchi M;Azuma M
• 通讯作者: Azuma M

Overexpression of B7-H1 on epidermal keratinocytes promotes squamous cell carcinoma formation.

B7-H1 在表皮角质形成细胞上的过度表达可促进鳞状细胞癌的形成。

• 发表时间: 2010
• 作者: Cao Y;Zhang L;Ritprajak P;Hashiguchi M;Azuma M
• 通讯作者: Azuma M

Enhancement of effector CD8^+ T cell function by tumor-associated B7-H3 and modulation of its counter receptor triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) at tumor sites.

通过肿瘤相关的 B7-H3 增强效应 CD8^ T 细胞功能，并调节其反受体触发肿瘤部位骨髓细胞样转录物 2 (TLT-2) 上表达的受体。

• 发表时间: 2010
• 作者: Kobori H;Hashiguchi M;Azuma M
• 通讯作者: Azuma M

Binding property, expression, and function of human TLT2,a counter-receptor for B7-H3.

人 TLT2（B7-H3 的反受体）的结合特性、表达和功能。

• 发表时间: 2009
• 作者: Hashiguchi M;Kobori H;Azuma M
• 通讯作者: Azuma M

Essential roles of B7-H1 and B7-DC expressed on mesenteric dendritic cells in oral tolerance

肠系膜树突状细胞上表达的 B7-H1 和 B7-DC 在口服耐受中的重要作用

• 发表时间: 2009
• 作者: Takagi H;Fukaya T;Azuma M;et al.
• 通讯作者: et al.