Functional analysis of costimulatory molecules in oral diseases and their intervention for clinical application

口腔疾病共刺激分子的功能分析及其临床干预应用

• 批准号: 13854021
• 负责人: AZUMA Miyuki
• 金额: $ 69.47万
• 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 (S)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13854021/
• 关键词: Immunology; Dentistry; Infectious diseases; Cancer; Costimulatory molecules; Oral diseases; Dendritic cells; T lymphocytes; 口腔粘膜疾患; 免疫制御; 歯髄; 粘膜上皮細胞; 免疫; 歯髄炎; 骨吸収; 補助シグナル; 破骨細胞; 細胞間相互作用

We investigated expression and function of costimulatory molecules including PD-1:B7-H1/B7-DC, ICOS:B7h, BTLA, B7-H3, and B7-H3 in oral immune responses and diseases. B7-H1 that is one of ligands for PD-1 was induced on a various inflammatory tissue cells as well as immune cells, whereas expression of B7-DC was limited on activated dendritic cells (DCs) and macrophages. Our results demonstrate the involvement of PD-1:B7-H1 pathway in immune regulation based on the studies from the comparative analyses between expression and clinical features and prognosis in oral lichen planus (OLP) and oral cancer, and in addition, the in vivo treatments with blocking monoclonal antibodies in models of skin contact hypersensitivity and oral cancer. A ligand of ICOS, B7h was less expressed as compared with B7-H1, but was expressed at high levels on endothelial cells in OLP and oral cancer tissues, suggesting the involvement of B7h in lymphocyte infiltration into the tissues.We have established a murine … More pulpitis model using fresh-frozen decalcified hard tissue sections and an immunofluorescence staining and examined dental pulp after dentin exposure. We found that two types of DCs, CD11c^+F4/80^- and CD11c^-F4/80^+, exist in dental pulp. CD11c^+F4/80^- cells located in the pulp-dentin border and expressed constitutively TLR2, TLR4, and CD205. CD11c^-F4/80^+ cells located in the central pulp and were lacking the above molecules. Both types of cells migrated rapidly to the P-D border of treated cusp side, but a part of F4/80^+ cells alone induced a costimulatory molecule CD86. Simultaneously, F4/80^+CD86^+ cells in the regional lymph nodes increased, suggesting the migration of these cells from the pulp. These results suggest that antigen-capture and migration of pulpal DCs may occur and the migrated DCs may induce a consequent adoptive immune response. Our findings provide important information for estimating the healing properties of dental pulp and for developing possible treatments of dental restoration. Less

我们研究了包括PD-1：B7-H1/B7-DC，ICOS：B7H，BTLA，B7-H3和B7-H3在包括PD-1：B7-H1/B7-DC在内的共刺激分子的表达和功能。 B7-H1是PD-1配体之一的B7-H1，在多种炎性组织细胞以及免疫细胞上诱导，而B7-DC的表达受到活化的树突状细胞（DCS）和巨噬细胞的限制。我们的结果证明了PD-1：B7-H1途径在免疫学中的参与，这是根据表达和临床特征之间的比较分析以及口腔扁平乳胸膜（OLP）和口腔癌的预后的研究，此外，还具有封闭的单克隆抗体的体内治疗，从而在皮肤接触性抗体中封闭了单克隆抗体。 A ligand of ICOS, B7h was less expressed as compared with B7-H1, but was expressed at high levels on endothelial cells in OLP and oral Cancer tissues, suggesting the involvement of B7h in lymphocyte infiltration into the tissues.We have established a murine … More pulpitis model using fresh-frozen decalcified hard tissue sections and an immunofluorescence staining and examined dental牙本接触后的果肉。我们发现牙纸浆中存在两种类型的DC，CD11C^+F4/80^ - 和CD11C^-F4/80^+。 CD11C^+F4/80^ - 位于纸浆 - 丁丁边界中的细胞，并表达了组成性的TLR2，TLR4和CD205。 CD11C^-F4/80^+细胞位于中央纸浆中，缺乏上述分子。两种类型的细胞迅速迁移到处理过的尖尖的p-d边界，但单独的F4/80^+细胞的一部分诱导了共刺激分子CD86。同时，区域淋巴结中的F4/80^+ CD86^+细胞增加，表明这些细胞从纸浆中迁移。这些结果表明，牙髓DC的抗原捕获和迁移可能会发生，并且迁移的DC可能导致采用的免疫响应。我们的发现提供了重要的信息，用于估计牙髓的愈合特性以及开发牙齿恢复的可能治疗方法。较少的

项目成果

B7-H1 expression in non-small cell lung cancer and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

B7-H1在非小细胞肺癌中的表达及其与肿瘤浸润淋巴细胞及其PD-1表达的关系。

• 发表时间: 2004
• 期刊: Clin Cancer Res 10
• 作者: Konishi J;Yamazaki K;Azuma M;Kinoshita I;Dosaka-Akita H;Nishimura M.
• 通讯作者: Nishimura M.

Subcutaneous injection of a TNF-a antagonist peptide inhibit both inflammation and bone resorption in collagen-induced murine arthritis.

皮下注射 TNF-α 拮抗剂肽可抑制胶原诱导的小鼠关节炎的炎症和骨吸收。

• 发表时间: 2005
• 期刊: J. Med. Dent. Sci 52
• 作者: Kojima T;Aoki K;Nonaka K;Saito H;Azuma M;Iwai H;Varghese BJ.;Yoshimatsu H.;Baron R;Ohya K;Amagasa T.
• 通讯作者: Amagasa T.

Amelioration of collagen-induced arthritis by blockade of ICOS-B7h costimulation.

通过阻断 ICOS-B7h 共刺激来改善胶原诱导的关节炎。

• 发表时间: 2002
• 期刊: J Immunol. 169
• 作者: Iwai H.;Kozono Y;Hirose S;Akiba H;Yagita H;Okumura K;Kohsaka H;Miyasaka N;Azuma M.
• 通讯作者: Azuma M.

A critical role for the programmed death ligand l in fetomaternal tolerance.

程序性死亡配体 l 在母胎耐受中发挥关键作用。

• 发表时间: 2005
• 期刊: J. Exp. Med 202
• 作者: Guleria I;Khousroshahi A;Ansari MJ;Habicht A;Azuma M;Yagita H;Noelle RJ;Coyle A;Mellor AL;Khoury SJ;Sayegh MH
• 通讯作者: Sayegh MH

The effect of recombinant CD80-Adenovirus and interleukin-12 on generation of cytotoxic T lymphocytes against autologous tumour in patients with oral squamous cell carcinoma.

重组CD80腺病毒和白细胞介素12对口腔鳞状细胞癌患者体内抗自体肿瘤的细胞毒性T淋巴细胞产生的影响。

• 发表时间: 2002
• 期刊: Asian J Oral Maxillofac Surg. 14
• 作者: Mogi S;Ebata T;Toda H;Hirano Y;Enomoto S;Azuma M.
• 通讯作者: Azuma M.