Mechanisms to facilitate the development of autoimmune arthritis by over-expression of HTLV-1pX.
| Project/Area Number |
15590439
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
ISHIHARA Katsuhiko Osaka University, Graduate School of Frontier Biosciences, Associate Professor, 生命機能研究科, 助教授 (10263245)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | IL-6 / gp130 / mouse models / STAT3 / Rheumatoid arthritis / HTLV-1 / pX / dendritic cell / ノックインマウス / 自己免疫疾患マウスモデル / HTLV-1pX / トランスジェニックマウス |
|---|
| Research Abstract |
We generated a double-mutant mouse by crossing two murine models of RA, a gp 130 mutant knock-in mouse (gp130^<F759/F759>) and an HTLV-1 pX transgenic mouse (pX-Tg), in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously developed severe arthritis with a much earlier onset than the gp130^<F759/F759> mice and with a much higher incidence than did the pX-Tg mice. The symptoms of gp130^<F759/F759> mice, including lymphoadenopathy, splenomegaly, hyper-γ-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHC^<bright> CD11c^+ population, were augmented in the double mutants. Immunohistochemical analyses revealed production of IL-6 and nuclear translocation of phospho-STAT3 in the macrophages and fibroblasts in the synovium of arthritic joints. CD4^+ T cells are closely located to the class II MHC molecules expressed by CD11b^+ cells in the synovium. Marked reductions in incidence, severity, and immunological abnormalities were seen in the triple mutant, IL-6^<-/->/gp130^<F759/F759>/pX-Tg, indicating that the arthritis in the double mutant is IL-6 dependent. Inhibitory effects on the maturation of dendritic cells by IL-6/STAT3 signal were demonstrated in vivo and in vitro. Experiments of bone marrow transfer revealed that both the gp130^<F759/F759> mutation and over-expression of pX gene in the non-hematopoietic cells but not in hematopoietic cells are required for the development of arthritis.
|
Report
(3 results)
Research Products
(16 results)
