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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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Keywords | 炎症性腸疾患 / 新規治療法 / 免疫統御 / 腸内細菌 / メモリーT細胞 / プロバイオテ / 免疫学的加齢 / プロバイオティクス |
|---|
| 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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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis.2010
Author(s)
Mikami Y, Kanai T, Sujino T, Ono Y, Hayashi A, Okazawa A, Kamada N, Matsuoka K, Hisamatsu T, Okamoto S, Takaishi H, Inoue N, Ogata H, Hibi T.
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Journal Title
Eur J Immunol.
Volume: 40
Pages: 2409-2422
Related Report
Peer Reviewed
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[Journal Article] Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn's disease.2010
Author(s)
Takayama T, Kamada N, Chinen H, Okamoto S, Kitazume MT, Chang J, Matuzaki Y, Suzuki S, Sugita A, Koganei K, Hisamatsu T, Kanai T, Hibi T.
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Journal Title
Gastroenterology
Volume: 139
Pages: 882-892
Related Report
Peer Reviewed
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[Journal Article] Monocyte chemoattractant protein-1 contributes to gut homeostasis and intestinal inflammation by composition of IL-10-producing regulatory macrophage subset.2010
Author(s)
Takada Y, Hisamatsu T, Kamada N, Kitazume MT, Honda H, Oshima Y, Saito R, Takayama T, Kobayashi T, Chinen H, Mikami Y, Kanai T, Okamoto S, Hibi T.
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Journal Title
J Immunol.
Volume: 184
Pages: 2671-2676
Related Report
Peer Reviewed
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[Journal Article] MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis.2010
Author(s)
Ojiro K, Ebinuma H, Nakamoto N, Wakabayashi K, Mikami Y, Ono Y, Po-Sung C, Usui S, Umeda R, Takaishi H, Yamagishi Y, Saito H, Kanai T, Hibi T.
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Journal Title
Biochem Biophys Res Commun.
Volume: 399
Pages: 744-749
Related Report
Peer Reviewed
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[Journal Article] Human CD14+ macrophages in intestinal lamina propria exhibit potent antigen-presenting ability2009
Author(s)
Kamada N, Hisamatsu T, Honda H, Kobayashi T, Chinen H, Kitazume MT, Takayama T, Okamoto S, Koganei K, Sugita A, Kanai T, Hibi T.
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Journal Title
J Immunol. 183
Pages: 1724-1731
Related Report
Peer Reviewed
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[Journal Article] Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis2009
Author(s)
Nemoto Y, Kanai T, Kameyama K, Shinohara T, Sakamoto N, Totsuka T, Okamoto R, Tsuchiya K, Nakamura T, Sudo T, Matsumoto S, Watanabe M.
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Journal Title
J Immunol. 183
Pages: 5059-5068
Related Report
Peer Reviewed
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[Journal Article] RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis2009
Author(s)
Totsuka T, Kanai T, Nemoto Y, Tomita T, Okamoto R, Tsuchiya K, Nakamura T, Sakamoto N, Akiba H, Okumura K, Yagita H, Watanabe M.
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Journal Title
J Immunol. 182
Pages: 6079-6087
Related Report
Peer Reviewed
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[Journal Article] Signaling pathway via TNFα/NFκB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis2009
Author(s)
Onizawa M, Nagaishi T, Kanai T, Oshima S, Nemoto Y, Yoshioka A, Totsuka T, Okamoto R, Nakamura T, Sakamoto N, Tsuchiya K, Yagita H, Watanabe M.
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Journal Title
Am J Physiol Gastrointest Liver Physiol. 296
Related Report
Peer Reviewed
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