| Project/Area Number |
07557032
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 試験 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Tokyo Medical and Dental University (1996)
Kyoto University (1995) |
|---|
Principal Investigator |
TSUBATA Takeshi Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80197756)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIYAWAKI Shigeki Nippon Shinyaku Co.Ltd., Manager, 分子生物学研究部, 課長
ISHIDA Hiroshi Utano National Hospital, Clinical Research Center, Chief, 臨床研究部, 室長
HONJO Tasuku Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (80090504)
HIAI Hiroshi Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (10073131)
|
|---|
| Project Period (FY) |
1995 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | aly mouse / autoimmune disease / exocrine organs / Sjogren's syndrome / CD4^+ T cells / IL-10 / animal model / chronic pancreatitis / 自己免疫 |
|---|
| Research Abstract |
Mice homozygous for an autosomal recessive mutation aly (alymphoplasia) lack both lymph nodes and Peyer's patches, and show defects in both humoral and cellular immunity. Histopathological analysis revealed chronic inflammatory changes in exocrine organs such as the salivery gland, lacrimal gland and pancreas of the homozygotes (aly/aly) but not the heterozygotes (aly/+). In these exocrine organs, mononuclear cells consisting mainly of CD4^+ T cells infiltrate periductal areas, and, in some cases, the cell infiltration extended to lobules. Inflammatory changes were also observed in the lung of the homozygotes. Because we maintained the aly mice by mating the homozygotes with heterozygotes. Because we maintained the aly mice by mating the homozygotes with heterozygotes, the association of the inflammatory changes to homozygotes strongly suggest that the lesions are caused by aly mutation itself or the gene close to the aly gene. Since Sjogren's syndrome is characterized by diffuse lymph
… More
ocyte infiltration in the periductal areas of the lacrimal and salivary glands and is occasionally associated with pulmonary disease, aly/aly mice may serve as a unique single gene model of Sjogren's syndrome.
The inflammatory changes in exocrine organs were transferred by a CD4^+ T cell-enriched fraction of spleen cells from homozygous animals. These results suggest that autoimmune mechanisms mediated by self-reactive T cells may be involved in the inflammatory lesions of various exocrine organs in the homozygous mice although these mice show immunodeficiency. We further assessed the role of cytokines controling Th1 differentiation such as IL-10. When we treated aly/aly mice with anti-IL-10, the severity of the inflammatory changes in the exocrine organes were significantly reduced. This result indicates that IL-10 play some roles in the pathogenesis of the inlammation of the exocrine organs in aly mice and suggests that Sjogren syndrome may be treated by blocking the activity of IL-10. Less
|
