Immune regulation on autoimmune and allergic diseases by the TIM family molecules
Project/Area Number |
26293087
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Juntendo University |
Principal Investigator |
Okumura Ko 順天堂大学, 医学部, 教授 (50009700)
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Co-Investigator(Kenkyū-buntansha) |
秋葉 久弥 順天堂大学, 医学(系)研究科(研究院), 准教授 (60338316)
|
Co-Investigator(Renkei-kenkyūsha) |
KOJIMA Yuko 順天堂大学, 医学研究科, 助教 (60231312)
|
Research Collaborator |
KAMACHI Fumitaka
HARADA Norihiro
ABE Yoshiyuki
ISSHIKI Takuma
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Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
|
Keywords | 免疫学 / 自己免疫疾患 / アレルギー疾患 / 炎症 / アレルギー・ぜんそく |
Outline of Final Research Achievements |
In this study, we investigated the effects of anti-TIM-4 mAb in a murine model of mast cell-dependent anaphylaxis and lung inflammation. Accumulation of eosinophils and production of Th2 cytokines in the lung were significantly reduced in the anti-TIM-4-treated mice. We confirmed that TIM-4 through proteolytic cleavage of cell surface TIM-4. Moreover, TIM-4 regulated the cytokine production, but not degranulation, by mast cells through the interaction with leukocyte mono-Ig-like receptor 5 (LMIR5) and TIM-3. Taken together, it is possible that TIM-4 can be an appropriate target for the therapeutic treatment and/or the diagnostic marker of allergic diseases.
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Academic Significance and Societal Importance of the Research Achievements |
現在、TNF-αなど個々の炎症性サイトカインを標的にした抗体医薬品は実用されているが、多種の炎症性サイトカイン産生を総合的に根本から抑制することが可能になれば、個々の抗サイトカイン抗体療法に抵抗性を持つ患者さんの治療に繋がる。また抗TIM-4抗体による抗炎症作用は、関節炎に留まらず、他の難治性慢性炎症疾患の新たな治療ターゲット分子になる可能性があり、またsTIM-4は補助診断あるいは治療効果や予後予測に際して有用なバイオマーカーになる可能性がある。
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Report
(4 results)
Research Products
(62 results)
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[Journal Article] Involvement of PU.1 in NFATc1 promoter function in osteoclast development2017
Author(s)
Ishiyama K, Yashiro T, Nakano N, Kasakura K, Miura R, Hara M, Kawai F, Maeda K, Tamura N, Okumura K, Ogawa H, Takasaki Y, Nishiyama C
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Journal Title
Allergol. Int.
Volume: 64(3)
Issue: 3
Pages: 241-247
DOI
NAID
ISSN
1323-8930, 1440-1592
Year and Date
2017-12-11
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Subcutaneous allergic sensitization to protease allergen is dependent on mast cells but not IL-33: Distinct mechanisms between subcutaneous and intranasal routes.2016
Author(s)
Kamijo S, Suzuki M, Hara M, Shimura S, Ochi H, Maruyama N, Matsuda A, Saito H, Nakae S, Suto H, Ichikawa S, Ikeda S, Ogawa H, Okumura K, Takai T.
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Journal Title
J Immunol.
Volume: 196
Pages: 3559-3569
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Epicutaneous Allergic Sensitization by Cooperation between Allergen Protease Activity and Mechanical Skin Barrier Damage in Mice2016
Author(s)
Shimura S, Takai T, Iida H, Maruyama N, Ochi H, Kamijo S, Nishioka I, Hara M, Matsuda A, Saito H, Nakae S, Ogawa H, Okumura K, Ikeda S.
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Journal Title
J Invest Dermatol.
Volume: 136
Pages: 1408-1417
DOI
NAID
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] A Pilot Study of Operational Tolerance with a Regulatory T Cell-Based Cell Therapy in Living Donor Liver Transplantation.2016
Author(s)
①Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T, Sato N, Sugita J, Hatanaka K, Bashuda H, Habu S, Demetris AJ, Okumura K
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Journal Title
Hepatology
Volume: 00
Pages: 00-00
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice2016
Author(s)
Suzuki M, Hara M, Ichikawa S, Kamijo S, Nakazawa T, Hatanaka H, Akiyama K, Ogawa H, Okumura K, Takai T
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Journal Title
Allergol. Int.
Volume: 65
Issue: 1
Pages: 44-51
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] he Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells.2015
Author(s)
Yamazaki S, Nakano N, Honjo A, Hara M, Maeda K, Nishiyama C, Kitaura J, Ohtsuka Y, Okumura K, Ogawa H, Shimizu T
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Journal Title
J Immunol.
Volume: 195(7)
Pages: 3427-3425
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice.2015
Author(s)
Morita H, Arae K, Unno H, Toyama S, Motomura K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Saito H, Matsumoto K, Nakae S.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 20. An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers.2015
Author(s)
Morita H, Arae K, Unno H, Miyauchi K, Toyama S, Nambu A, Oboki K, Ohno T, Motomura K, Matsuda A, Yamaguchi S, Narushima S, Kajiwara N, Iikura M, Suto H, McKenzie AN, Takahashi T, Karasuyama H, Okumura K, Azuma M, Moro K, Akdis CA, Galli SJ, Koyasu S, Kubo M, Sudo K, Saito H, Matsumoto K, Nakae S.
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Journal Title
Immunity.
Volume: 43
Pages: 175-186
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Characteristics of alveolar macrophages from murine models of OVA-induced allergic airway inflammation and LPS-induced acute airway inflammation.2015
Author(s)
1)Katsura Y, Harada N, Harada S, Ishimori A, Makino F, Ito J, Kamachi F, Okumura K, Akiba H, Atsuta R, Takahashi K
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Journal Title
Exp Lung Res
Volume: 41
Pages: 370-382
DOI
Related Report
Peer Reviewed
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[Journal Article] Notch signaling enhances FcεRI-mediated cytokine production by mast cells through direct and indirect mechanisms2015
Author(s)
Nakano, N., Nishiyama, C., Yagita, H., Hara, M., Motomura, Y., Kubo, M., Okumura, K., and Ogawa, H
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Journal Title
The Journal of Immunology
Volume: 194(9)
Pages: 4535-44
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Potential role of myeloid cell/eosinophil-derived IL-17 in LPS-induced endotoxin shock2014
Author(s)
Shimura E, Shibui A, Narushima S, Nambu A, Yamaguchi S, Akitsu A, Leonard WJ, Iwakura Y, Matsumoto K, Suto H, Okumura K, Sudo K, Nakae S
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Journal Title
Biochem Biophys Res Commun.
Volume: 453
Pages: 1-6
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Commensal bacteria regulate thymic Aire expression.2014
Author(s)
Nakajima A, Negishi N, Tsurui H, Kadowaki-Ohtsuji N, Maeda K, Nanno M, Yamaguchi Y, Shimizu N, Yagita H, Okumura K, Habu S.
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Journal Title
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner2014
Author(s)
Iida H, Takai T, Hirasawa Y, Kamijo S, Shimura S, Ochi H, Nishioka I, Maruyama N, Ogawa H, Okumura K, Ikeda S
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Journal Title
Allergol. Int.
Volume: 63
Issue: 2
Pages: 219-226
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Critical Roles for PU.1, GATA1, and GATA2 in the expression of human FcεRI on mast cells: PU.1 and GATA1 transactivate FCER1A, and GATA2 transactivates FCER1A and MS4A2.2014
Author(s)
Inage E, Kasakura K, Yashiro T, Suzuki R, Baba Y, Nakano N, Hara M, Tanabe A, Oboki K, Matsumoto K, Saito H, Niyonsaba F, Ohtsuka Y, Ogawa H, Okumura K, Shimizu T, and Nishiyama C
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Journal Title
J Immunol
Volume: 192
Pages: 3936-3946
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Host defense (antimicrobial) peptide, human beta-defensin-3, improves the function of the epithelial tight junction barrier in human keratinocytes2014
Author(s)
Kiatsurayanon C, Niyonsaba F, Smithrithee R, Akiyama T, Ushio H, Hara M, Okumura K, Ikeda S, Ogawa H.
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Journal Title
Journal of Investigative Dermatology
Volume: 143
Pages: 2163-2173
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] TSLP expression induced via Toll-like receptor pathways in human keratinocytes.2014
Author(s)
Takai T, Chen X, Xie Y, Vu AT, Le TA, Kinoshita H, Kawasaki J, Kamijo S, Hara M, Ushio H, Baba T, Hiramatsu K, Ikeda S, Ogawa H, Okumura K
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Journal Title
Methods Enzymol.
Volume: 535
Pages: 371-387
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Circadian Regulation of Allergic Reaction by the Mast Cell Clock.2014
Author(s)
Nakamura Y, Nakano N, Ishimaru K, Hara M, Ikegami T, Tahara Y, Katoh R, Ogawa H, Okumura K, Shibata S, Nishiyama C, Nakao A
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Journal Title
Journal of Allergy and Clinical Immunology
Volume: 133(2)
Pages: 568-575
DOI
Related Report
Peer Reviewed
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[Journal Article] Sphingomyelin and ceramide are physiological ligands for human LMIR3/CD300f, inhibiting FcεRI-mediated mast cell activation.2014
Author(s)
Izawa, K., Isobe, M., Matsukawa, T., Ito, S., Maehara, A., Takahashi, M., Yamanishi, Y., Kaitani, A., Oki, T., Okumura, K., *Kitamura, T., and *Kitaura, J.
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Journal Title
J Allergy Clin Immunol.
Volume: 133
Pages: 270-273
DOI
Related Report
Peer Reviewed
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[Presentation] The role of leukocyte mono-immunoglobulin -like receptor 8 (LMIR8)/CLM-6 in plasmacytoid dendritic cell (pDC)2016
Author(s)
KAITANI Ayako, IZAWA Kumi, MAEHARA Akie, ISOBE Masamichi, Takamori Ayako, Uchida Shino, NAKANO Nobuhiro, MAEDA Keiko, ANDO Tomoaki, OKUMURA Ko, KITAMURA Toshio, KITAURA Jiro
Organizer
第45回日本免疫学会
Place of Presentation
沖縄コンベンションセンター、ラグナガーデンホテル
Year and Date
2016-12-05
Related Report
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[Presentation] CD300f suppresses LPS-induced skin inflammation2016
Author(s)
Watanabe Daiki, IZAWA Kumi, KAITANI Ayako, MAEHARA Akie, ISOBE Masamichi, Takamori Ayako, Uchida Shino, NAKANO Nobuhiro, MAEDA Keiko, ANDO Tomoaki, OKUMURA Ko, KITAMURA Toshio, KITAURA Jiro
Organizer
第45回日本免疫学会
Place of Presentation
沖縄コンベンションセンター、ラグナガーデンホテル
Year and Date
2016-12-05
Related Report
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[Presentation] Leukocyte mono-immunoglobulin-like receptor 6 (LMIR6) is an activating receptor expressed in patrolling monocytes2016
Author(s)
ISOBE Masamichi, Takamori Ayako, IZAWA Kumi, MAEHARA Akie, KAITANI Ayako, Uchida Shino, NAKANO Nobuhiro, MAEDA Keiko, ANDO Tomoaki, OKUMURA Ko, KITAMURA Toshio, KITAURA Jiro
Organizer
第45回日本免疫学会
Place of Presentation
沖縄コンベンションセンター、ラグナガーデンホテル
Year and Date
2016-12-05
Related Report
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