2011 Fiscal Year Final Research Report
Permanent cure strategy of inflammatory bowel diseases by inducing immunological reset
| Project/Area Number |
21390233
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | 炎症性腸疾患 / 新規治療法 / 免疫統御 |
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| Research Abstract |
Despite the advent of an age when "malignant" leukemia is cured by bone marrow transplantation, "benign" inflammatory bowel diseases(IBD) are still intractable lifelong diseases. We showed that immune memory T cells that remember the disease are formed in IBD, and perceiving them as "benign T-cell leukemia"-like lifelong pathology that spreads throughout the body, We demonstrated that interleukin-7(IL-7) and commensal bacteria are essential as a survival factor for the maintenance and proliferation of colitogenic CD4^+memory T cells, in IBD. Although IL-17A is thought to be preferentially produced by T_h17 cells and to play a critical role in autoimmune disease development, it seems to inhibit development of T_h1 cells in some circumstances. Colitogenic T_h1 cells and T_h17 cells seem to interfere with each other in vivo under inflammatory conditions. At least in inflammatory conditions, colitogenic T_h1 cells and T_h17 cells are not independently generated ; rather the linear sequential developmental pathway from T_h17 to Th1 cells seems to dominate. Further study is needed to determine whether the classical T_h1 cells directly generated from naive T cells in an RORγt-independent manner are also involved in IBD pathogenesis. The pathway from T_h17/T_h1 cells to alternative T_h1 cells is suppressed by T_<reg> cells, resulting in the accumulation of T_h17 cells by T_<reg> cells.
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