2007 Fiscal Year Final Research Report Summary
Molecular mechanism and its regulation of heterophilic adhesion between α E 3 7 (CD103) and E-cadherin in autoimmune epithelial injury
| Project/Area Number |
18591122
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Saitama Medical University |
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Principal Investigator |
TAKEUCHI Tsutomu Saitama Medical University, Medicine, Professor (50179610)
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| Co-Investigator(Kenkyū-buntansha) |
TSUZAKA Kensei Saitama Medical University, Medicine, Assistant professor (00245490)
YOSHIMOTO Keiko Saitama Medical University, Medicine, investigator (20383292)
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| Project Period (FY) |
2006 – 2007
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| Keywords | autoimmunity / epithelial injuries / adherin / integrin / CD103 |
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| Research Abstract |
It is proposed that immuno-competent cells, which play an indispensable role in host defense in normal individuals, attack self tissues in autoimmune diseases. We have demonstrated that these immune cells are involving the tissue injuries as the effector cells not only in salivary gland destruction in Sjogren's syndrome, but also in interstitial alveolar damage in dermatomyositis, raising a hypothesis of autoimmune epithelitis. Given the observation that CD8+ T lymphocytes are infiltrated around the aciner epithelial cells and the CD8+ cells are expressing aEb7 (CD 103) adhesion molecules, it is suggested that these lymphocytes adhere to the epithelial cells through aEb7 and E-cadherin on the epithelial cells. However, the detailed molecular mechanism remains to be clarified. In this study, we focus on the aEb7 and E-cadherin adhesion and attempt to explore the immunological mechanism of autoimmune epithelial injuries. In addition, we investigate the efficient intervention of the adhesion for applying to the future clinical development. Monoclonal antibodies or peptide antagonist may be useful to inhibit the adhesion, but those may also interfere to homophilic adhesion between epithelial cells. To search the inhibitory modalities specifically block heterophilic adhesion between aEb7 and E-cadherin, but not homophilic adhesion, we generated a series of deletion mutant of wild type E-cadherins and established the L-cell transfectant expressing E-cadherin without each domains. Using these L-cells and transfectants with aE chain and b7 chasin of integrins, we identified that 5th domain is responsible for the heterophilic adhesion. On the basis of the findings, we examined expression of the aEb7 on the peripheral and tissue lymphocytes and E-cadherin in the inflamed tissues.
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[Journal Article] T The conservative sequences in 3' UTR of TCRtξ mRNA regulate the production of TCRξ and TCR/CD3 complex in SLE T cells.2008
Author(s)
Tsuzaka, K, Itami, Y, Kumazawa, C, Suzuki, M, Setoyama, Y, Yoshimoto, K, Suzuki, K, Abe, T, Takeuchi, T
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Journal Title
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「研究成果報告書概要(欧文)」より
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[Journal Article] Down-regulation of Fas-ligand mRNA Shogren' syndrome patients with enlarged exocrine glands2007
Author(s)
Tsuzaka, K, Matsumoto, Y, Sasaki, Y, Abe, T, Tsubota, K, Takeuchi, T
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Journal Title
Autoimmunity 40
Pages: 497-502
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prospective study of low dose cyclosporine A in patients with refractory lupus nephritis2007
Author(s)
Ogawa, H, Kameda, H, Nagasawa, H, Sekiguchi, N, Takei, H, Tsuzaka, K, Amano, K, d Takeuchi, T
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Journal Title
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[Journal Article] A muticenter phase I/II trial of rituximab for refractory systemic lupus erythematosus2007
Author(s)
Tanaka, Y, Yamamoto, K, Takeuchi, T, Nishimoto, N, Miyasaka, N, Sumida, T, Shima, Y, Takada, K, Matsumoto, I, Saito, K, Koike, T
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Journal Title
Mod Rheum 17
Pages: 191-7
Description
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[Journal Article] Efficacy and Safety of Tacrolimus in Patients with rheumatoid arthritis in clinical practice : Significant role of blood concentration measurement for preventing severe adverse events2007
Author(s)
Suzuki, K, Takei, H, Kameda, H, Nagasawa, H, Sekiguchi, N, Nishi, E, Ogawa, H, Tsuzaka, K, Amano, K, Takeuchi, T
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Journal Title
Arthritis Rheum S 35
Pages: CRCO3
Description
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[Journal Article] DNA microarray gene expression profile of T cells with splice variants of TCRz mRNA observed in SLE2006
Author(s)
Tsuzaka, K, Nozaki, K, Kumazawa, C, Shiraishi, K, Setoyama, Y, Yoshimoto, K, Suzuki, K, Abe, T, Takeuchi, T
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Journal Title
J Immunol 176
Pages: 949-56
Description
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[Journal Article] Aberrant expression of BAFF in T cells of systemic lupus erythematosus, which is recapitulated by a human T cell line, Loucy2006
Author(s)
Yoshimoto, K, Takahashi, Y, Ogasawara, M, Setoyama, Y, Suzuki, K, Tsuzaka, K, Abe, T, Takeuchi, T
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Journal Title
Int Immunol 18
Pages: 1189-96
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] TCRz mRNA splice variant forms observed in peripheral blood T cells from systemic lupus erythematosus patients2006
Author(s)
Tsuzaka, K, Nozaki, K, Kumazawa, C, Shiraishi, K, Setoyama, Y, Yoshimoto, K, Abe, T, Takeuchi, T
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Journal Title
Springer Seminars in Immunopathology 28
Pages: 185-93
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Efficacy and safety of tacrolimus in patients with rheumatic disease : Appropriate clinical application for various rheumatic conditions2007
Author(s)
Suzuki, K, Kameda, H, Amano, K, Nagasawa, H, Sekiguchi, N, Takei, H, Nishi, E, Okuyama, A, Ogawa, H, Tsuzaka, K, Takeuchi, T
Organizer
American College of Rheumatology 71st Annual Meeting
Place of Presentation
Boston, U. S. A
Year and Date
20071100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 14-kd protein binds to the conservative region in TCR zeta mRNA 3' UTR and regulates the production of TCR zeta and TCR/CD3 complex2007
Author(s)
Tsuzaka, K, Itami, Y, Kumazawa, C, Setoyama, Y, Yoshimoto, K, Suzuki, K, Abe, T, Takeuchi, T
Organizer
American College of Rheumatology 71st Annual Meeting
Place of Presentation
Boston, U. S. A
Year and Date
20071100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Possible involvement of MMP-9 in the production of BAFF in T cells2007
Author(s)
Yoshimoto, K, Setoyama, Y, Tsuzaka, K, Ogawa, Y, Tsubota, K, Abe, T, Takeuchi, T
Organizer
American uollege of Nheumatology Ylst Annual Meeting
Place of Presentation
Boston, U. S. A
Year and Date
20071100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Decreased expression of the glycosylated syndecan 4 accompanied with down-regulation of TCR zeta in SLE patient T cells2007
Author(s)
Tsuzaka, K, Itami, Y, Kumazawa, C, Setoyama, Y, Yoshimoto, K, Suzuki, K, Abe, T, Takeuchi, T
Organizer
American College of Rheumatology 71st Annual Meeting
Place of Presentation
Boston, U. S. A
Year and Date
20071100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] TCR ξ and TCR/CD3 expression from the TCR C mRNA with deleted form of the conservative sequences in 3' UTR is down-regulated due to its instability2007
Author(s)
Tsuzaka, K, Itami, Y, Kumazawa, C, Setoyama, Y, Yoshimoto, K, Suzuki, K, Abe, T, Takeuchi, T
Organizer
37th Japanese society for Immunology
Year and Date
20071100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Possible involvement of MMP in the production of soluble BAFF in human T cells2007
Author(s)
Yoshimoto, K, Takahashi, Y, Setoyama, Y, Suzuki, K, Tsuzaka, K, Abe, T, Takeuchi, T
Organizer
The EULAR annual congress of rheumatology, Barcelona
Place of Presentation
Spain
Year and Date
20070600
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Efficacy and Safety of Tacrolimus in Patients With Rheumatoid Arthritis in Clinical Practice : Significant Role of Blood Concentration Measurement for Preventing Severe Adverse Events2006
Author(s)
Suzuki, K, Takei, H, Kameda, H, Nagasawa, H, Sekiguchi, N, Nishi, E, Ogawa, H, Tsuzaka, K, Amano, K, Takeuchi, T
Organizer
70th Annual Meeting, Washington
Place of Presentation
D. C., U. S. A
Year and Date
20061100
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Responsible region in 3'UTR of TCRz mRNA for producing TCR/CD3 including TCRz in SLE T cells2006
Author(s)
Tsuzaka, K, Nozaki, K, Kumazawa, C, Setoyama, Y, Shiraishi, K, Abe, T, Takeuchi, T
Organizer
16th European Congress of Immunology
Place of Presentation
Paris, France
Year and Date
20060900
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Aberrant expression of BAFF in SLE T cells2006
Author(s)
Yoshimoto, K, Takahashi, Y, Setoyama, Y, Suzuki. K, Tsuzaka. K, Abe. T, Takeuchi, T
Organizer
The EULAR annual congress of rheumatology
Place of Presentation
Amsterdam, Holland
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より
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