| Project/Area Number |
21249090
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathobiological dentistry/Dental radiology
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
HAYASHI Yoshio 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 客員教授 (00127854)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ARAKAKI Rieko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (40231120)
YAMADA Akiko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (70452646)
ISHIMARU Naozumi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60314879)
新垣 理恵子 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (00193061)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥46,150,000 (Direct Cost: ¥35,500,000、Indirect Cost: ¥10,650,000)
Fiscal Year 2011: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2010: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2009: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
|
|---|
| Keywords | シェーグレン症候群 / 自己免疫疾患 / 治療法開発 / RbAp48 / CCR7 / エストロゲン / アロマターゼ / RNA干渉 / カテプシンL |
|---|
| Research Abstract |
We reported that transgenic(TG) expression of RbAp48, and CCR7 knockout(KO) mice resulted in the development of autoimmune exocrinopathy resembling Sjogren' s syndrome. CD4^+ T cell-mediated autoimmune lesions were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-γand interleukin-18, which activates interferon regulatory factor-1(IRF-1), and class II transactivator(CIITA). Regulatory T(Treg) cells were significantly retained in the lymph nodes of CCR7KO mice, and failed to patrol within the exocrine organs to protect autoimmunity. The gene targeting for RbAp48 with application of in vivo siRNA administration prevented autoimmune lesions. These results indicate a novel immunocompetent role of epithelial cells, resulting in loss of local tolerance prior to developing gender-based autoimmunity.
|
