2005 Fiscal Year Final Research Report Summary
Regulation of infectious immunity by the OX40-0X4OL system
| Project/Area Number |
13226006
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
SUGAMURA Kazuo Tohoku Univ, Grad Sch of Med, Professor, 大学院・医学系研究科, 教授 (20117360)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHII Naoto Tohoku Univ, Grad Sch of Med, Associate Professor, 大学院・医学系研究科, 助教授 (60291267)
|
|---|
| Project Period (FY) |
2001 – 2005
|
| Keywords | OX40 (CD134) / Inflammatory bowel disease / Linkage analysis |
|---|
| Research Abstract |
OX40-0X4OL interactions regulate survival and homeostasis of CD4+ T cells. Furthermore, several reports have demonstrated that OX40 signaling in T cells mediates not only autoimmune/inflammatory responses, but also infectious immunity by regulating T cell immunity. Interestingly, C57BL/6 OX40L-transgenic mice, which were constructed by using mouse lck proximal promoter, showed susceptibility to L. major infection although C57BL/6 wild-type mice are resistant to the infection. Since IL-13-deficiency in OX40L-transgenic mice recovered the susceptibility, IL-13 production induced by OX40 signals may mediates the susceptibility to L. major infection. In addition, OX40L-transgenic mice spontaneously develop organ-specific immune-associated diseases, namely interstitial pneumonia and inflammatory bowel disease (IBD). Studies using the OX40L-transgenic mice have demonstrated that OX40 signaling prominently affected the sensitivity of T cells to CD25+ regulatory-T-cell-mediated suppression, leading to IBD. Further investigation revealed that the development of IBD requires intestinal bacterial flora. Interestingly, IBD develops in a C57BL/6 strain-dependent manner. Thus, we have attempted to identify susceptibility genes for IBD seen in OX40L-Tg mice. A QTL analysis using the susceptible strain (C57BL/6) and a resistant strain (BALB/c) revealed a susceptibility locus on Ch. 4, which is syntenic to a human IBD-susceptibility locus (IBD7). These results suggest that a certain gene in this locus contributes to IBD development, which is associated with intestinal immunity to the bacterial flora.
|
