| Project/Area Number |
09307006
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
KIYONO Hiroshi Osaka U, Res, Inst.Microbial Dis., Professor, 微生物病研究所, 教授 (10271032)
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| Co-Investigator(Kenkyū-buntansha) |
KWEON Mi-na Osaka U, Res, Inst.Microbial Dis., Research Associate, 微生物病研究所, 助手 (80324846)
HIROI Takachika Osaka U, Res, Inst.Microbial Dis., Research Associate, 微生物病研究所, 助手 (80228824)
TAKAHASHI Ichiro Osaka U, Res, Inst.Microbial Dis., Assistant Professor, 微生物病研究所, 講師 (20206791)
YAMAMOTO Masafumi Nihon U.Sch. Dent. Matsudo, Assistant Professor, 松戸歯学部, 講師 (80210558)
島岡 要 大阪大学, 医学部, 助手 (40281133)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥30,500,000 (Direct Cost: ¥30,500,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1997: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Mucosal immune system / Mucosal intranet / Epithelial cell / Mucosal T cells / IgA / Peyer's patch / B-1 / B-2 cells / 粘膜細胞間インターネット / 粘膜細胞間イントラネット / 粘膜免疫機構 / 粘膜誘導型寛容 / 経口免疫寛容 / 粘膜系γδT細胞 / TCRδ遺伝子欠損マウス / IL-10 / 上皮細胞間リンパ球 / IgA / コレラ毒素 / IL-7 / IL-7R / γδT細胞 / 上皮細胞 |
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| Research Abstract |
The common mucosal immune system (CMIS) has been shown to be a key element which bridges between inductive (e.g. PP in the intestinal tract) and effector (e.g. i-LP) tissues for the induction of antigen-specific IgA response. However, our recent investigations provided new evidence that the IgA antibody response can be induced in an CMIS-independent manner via a B-1 lineage of IgA committed B cells. In contrast to the CMIS-dependent B-2 cells (IL-5R^+ and IL-6R^+), B-1 cells are under the regulation of a T cell independent cytokine IL-15/IL-15R signaling cascade in addition to the Th2 type IL-5/IL-5R pathway. These findings suggest that the mucosal immune system is equipped with both CMIS-dependent (B-2) and-independent (B-1) pathways for the induction of an IgA responses.
For the induction of chronic inflammation in the large intestine, we showed that immunopathological lymphocytes were a unique subset of thymus derived mucosal ββ T cells of the Th2-type (i.e. IL-4 producer). Removal of these cells by treatment With mAbs specific for TCRβ3 and IL-4 resulted in the inhibition of colitis development. With regard to intestinal allergy, our new OVA-induced model provides the first direct evidence that a Th2-type cell mediated local accumulation of mast cells, eosinophils, and IgE plasma cells in colon is associated with the induction of allergic symptoms. Further, it was shown that systemically originating antigen-specific Th2-type cells preferentially homed to the large intestine for STAT6-mediated IL-4 and IL-13 synthesis. Although chronic inflammation and allergic reaction represent two totally different immunological diseases, an interesting aspect of our findings is that CD4^+ T cells originating from the systemic compartment played a key role in the development of a disease condition in a remote mucosal compartment such as the large intestine.
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