| Project/Area Number |
20592217
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital |
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Principal Investigator |
SUZUKI Ryuji Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, 診断・治療研究室, 室長 (70373470)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Naoshi 独立行政法人国立病院機構(相模原病院臨床研究センター), 病態総合研究部, 研究部長 (10251258)
濱田 良樹 鶴見大学, 歯学部, 講師 (70247336)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 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 |
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| Research Abstract |
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
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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
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