T cell receptor analysis in oral lichen planus

口腔扁平苔藓的 T 细胞受体分析

• 批准号: 20592217
• 负责人: SUZUKI Ryuji
• 金额: $ 3万
• 依托单位: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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/grant/KAKENHI-PROJECT-20592217/
• 关键词: 口腔扁平苔癬; T細胞受容体; T細胞レセプター; 粘膜免役; 腫瘍; TCRレパトア; 口腔粘膜増生; 癌化; 病態解明

Oral lichen planus (OLP) is a refractory disorder of the oral mucosa, and develops via a T cell-mediated immune process. Here, we examined the characteristics of the infiltrating T cells in terms of the T cell receptor (TCR) repertoires, T cell clonality, T cell phenotypes and cytokine production profiles. TCR repertoire analyses and CDR3 size spectratyping were performed using PBMCs and tissue specimens of OLP biopsies from 12 patients. The cytokine expression profiles and T cell phenotypes were measured by real-time quantitative polymerase chain reaction. The expressions of 4 EGFR-like receptors and 6 EGF-like ligands were measured in OLP tissues from 10 patients and compared with the levels in normal oral mucosa (NOM) from 10 healthy donors. We observed that there were skewed TCR repertoires in the tissue samples (TCRVA8-1, VA22-1, VB2-1, VB3-1 and VB5-1) and PBMCs (TCRVA8-1, VB2-1, VB3-1 and VB5-1) from OLP patients. Furthermore, the CDR3 distributions in the skewed TCR subfamilies … More exhibited polyclonal patterns. We observed increases in CD4+T lymphocytes, IL-5, TNF-a and human leucocyte antigen D-related in the OLP tissue specimens. Of the receptors, only EGFR mRNA and protein were more highly expressed in OLP compared with NOM tissues. Regarding the ligands, the mRNAs of amphiregulin (AREG), epiregulin (EREG), and heparin-binding EGF-like growth factor (HB-EGF) were more highly expressed in OLP compared with NOM tissues. These ligands were strongly expressed by infiltrating lamina propria lymphocytes as well as epithelial keratinocytes in OLP lesions, as shown by immunohistochemistry. Taken together, the present results suggest that T cells bearing these TCRs are involved in the pathogenesis of OLP, and that IL-5 and TNF-a may participate in its inflammatory process.The enhanced EGFR expression on the keratinocytes in OLP lesions and the up-regulation of EGF-like ligands in keratinocytes and infiltrating mononuclear cells could contribute to the carcinogenesis and pathogenesis of OLP. Less

口腔扁平苔藓(OLP)是一种顽固性口腔黏膜疾病，通过T细胞介导的免疫过程发生。在这里，我们从T细胞受体(TCR)谱系、T细胞克隆性、T细胞表型和细胞因子产生谱等方面检测了浸润性T细胞的特征。对12例口腔扁平苔藓患者的PBMC和组织标本进行TCR谱系分析和CDR3大小分型。用实时定量聚合酶链式反应检测细胞因子表达谱和T细胞表型。检测10例口腔扁平苔藓患者口腔扁平苔藓组织中4种EGFR样受体和6种EGF样配体的表达，并与10例正常口腔黏膜(NOM)中的表达进行比较。我们观察到口腔扁平苔藓患者的组织标本(TCRVA8-1、VA22-1、VB2-1、VB3-1和VB5-1)和PBMC(TCRVA8-1、VB2-1、VB3-1和VB5-1)中存在偏斜的TCR谱带。此外，CDR3在偏斜TCR子家族…中的分布更多的细胞呈多克隆模式。我们观察到口腔扁平苔藓组织标本中CD4+T淋巴细胞、IL-5、TNF-α和人类白细胞抗原D相关水平的升高。在这些受体中，只有EGFR在口腔扁平苔藓组织中的表达高于正常组织。在配体方面，OLP组织中双调节蛋白(AREG)、表观调节蛋白(Ereg)和肝素结合的EGF样生长因子(HB-EGF)的mRNAs较正常组织高表达。免疫组织化学显示，这些配体在口腔扁平苔藓皮损中的固有层淋巴细胞和上皮角质形成细胞中呈强阳性表达。综上所述，上述结果提示，携带这些TCRs的T细胞参与了OLP的发病过程，IL-5和TNF-α可能参与了OLP的炎症过程。OLP皮损中角质形成细胞EGFR表达增强，角质形成细胞和浸润性单核细胞中EGF样配体表达上调，可能参与了OLP的发生和发展。较少

项目成果

Evidence for the changes of antitumor immune response during lymph node metastasis in head and neck squamous cell carcinoma

• DOI: 10.1016/j.tripleo.2010.03.030
• 发表时间: 2010-09-01
• 期刊: ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
• 作者: Kumagai, Kenichi;Hamada, Yoshiki;Suzuki, Ryuji
• 通讯作者: Suzuki, Ryuji

口腔扁平苔癬及び白板症におけるEGFR familyの網羅的解析

口腔扁平苔藓和白斑中EGFR家族的综合分析

• 发表时间: 2011
• 作者: 小林浩;熊谷賢一;江口貴紀;重松宏昭;濱田良樹;鈴木さつき;鈴木隆二
• 通讯作者: 鈴木隆二

Up-regulation of EGF receptor in keratinocytes and its ligands in infiltrating lymphocytes in the lesions of oral lichen planus

口腔扁平苔藓皮损角质形成细胞及其配体浸润淋巴细胞EGF受体上调

• 发表时间: 2010
• 期刊: Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110(6)
• 作者: Kenichi Kumagai;Tatsuya Horikawa;Akito Gotoh;Shoji Yamane;Hiroyuki Yamada;Hiroshi Kobayashi;Yoshiki Hamada;Ryuji Suzuki.
• 通讯作者: Ryuji Suzuki.

T Cell Recerptor Analysis of Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma

头颈鳞状细胞癌淋巴结转移的 T 细胞受体分析

• 发表时间: 2009
• 作者: 熊谷賢一;鈴木隆二
• 通讯作者: 鈴木隆二

The pathogenesis of oral lichen planus via epidermal growth factor receptor signaling

通过表皮生长因子受体信号传导口腔扁平苔藓的发病机制

• 发表时间: 2010
• 作者: Kenichi Kumagai;Horikawa T;Gotoh A;Yamane S;Yamada H;Kobayashi H;Eguchi T;Hamada Y;Suzuki R
• 通讯作者: Suzuki R