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Identification and functional analysis of a novel IL-6/IL-12 family cytokine

Research Project

Project/Area Number 15K08433
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionTokyo Medical University

Principal Investigator

Xu Mingli  東京医科大学, 医学部, 客員講師 (80597964)

Co-Investigator(Kenkyū-buntansha) 善本 隆之  東京医科大学, 医学部, 教授 (80202406)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsEBI3 / p19 / heterodimeric cytokine / IL-27 / IL-23
Outline of Final Research Achievements

In the present study, we elucidated that Epstein-Barr virus-induced gene 3 (EBI3), a common subunit of IL-27 and IL-35, and p19, one of IL-23 subunits can form a functional heterodimeric cytokine. EBI3 was first revealed to associate with p19, and subsequently hydrodynamic injection of the expression vector of a single chain of EBI3/p19 into mice was shown to augment an antigen-specific production of cytokines such as IL-17 and granulocyte-macrophage colony-stimulating factor in the draining lymph node cells. Then, transgenic mice over expressing the single chain of EBI3/p19 were established and exhibited resistance to the development of autoimmune hepatitis induced by injection with concanavalin A. Moreover, using a transplantable mouse tumor model of melanoma B16F10, EBI3/p19 was demonstrated to show potent antitumor activity. Currently, more detailed analysis on the molecular mechanism and its physiological role is under investigation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (19 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Int'l Joint Research] Merck Research Laboratories(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Interleukin-27 exerts its antitumor effects by promoting differentiation of hematopoietic stem cells to M1 macrophages.2018

    • Author(s)
      Chiba Y, Mizoguchi I, Furusawa J, Hasegawa H, Ohashi M, Xu M, Owaki T, Yoshimoto T.
    • Journal Title

      Cancer Res.

      Volume: 78 Issue: 1 Pages: 182-194

    • DOI

      10.1158/0008-5472.can-17-0960

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases.2018

    • Author(s)
      Chiba Y, Mizoguchi I, Hasegawa H, Ohashi M, Orii N, Nagai T, Sugahara M, Miyamoto Y, Xu M, Owaki T, Yoshimoto T.
    • Journal Title

      Cell. Mol. Life Sci.

      Volume: 75 Issue: 8 Pages: 1363-1376

    • DOI

      10.1007/s00018-017-2724-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective effects against tumors and infection by IL-27 through promotion of expansion and differentiation of hematopoietic stem cells into myeloid progenitors.2018

    • Author(s)
      Orii N, Mizoguchi I, Chiba Y, Hasegawa H, Ohashi M, Xu M, Nagai T, Ochiai M, Mochizuki Y, Owaki T, Yoshimoto T.
    • Journal Title

      Oncoimmunology

      Volume: - Issue: 5 Pages: e1421892-e1421892

    • DOI

      10.1080/2162402x.2017.1421892

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of chemical respiratory and contact sensitizers by OX40L expression in dendritic cells using a novel 3D co-culture system.2017

    • Author(s)
      Mizoguchi I, Ohashi M, Chiba Y, Hasegawa H, Xu M, Owaki T, Yoshimoto T.
    • Journal Title

      Front. Immunol.

      Volume: 8 Pages: 929-929

    • DOI

      10.3389/fimmu.2017.00929

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12 Heterodimeric Cytokine Family2016

    • Author(s)
      Hasegawa Hideaki, Izuru Mizoguchi, Yukino Chiba, Mio Ohashi, Mingli Xu, and Takayuki Yoshimoto
    • Journal Title

      Frontires in Immunolgy

      Volume: -

    • DOI

      10.3389/fimmu.2016.00479

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IL-17A-producing CD30(+) Vδ1 T cells drive inflammation-induced cancer progression.2016

    • Author(s)
      Kimura Y, Nagai N, Tsunekawa N, Sato-Matsushita M, Yoshimoto T, Cua DJ, Iwakura Y, Yagita H, Okada F, Tahara H, Saiki I, Irimura T, Hayakawa Y.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 9 Pages: 1206-14

    • DOI

      10.1111/cas.13005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expansion and differentiation of hematopoietic stem cells by IL-27 into myeloid progenitors to control infection2016

    • Author(s)
      Furusawa J-I, Mizoguchi I, Chiba Y, Hisada M, Kobayashi F, Yoshida H, Nakae S, Tshuchida A, Matsumoto T, Ema H, Mizuguchi J, Yoshimoto T
    • Journal Title

      PLoS Pathogen

      Volume: 12 Issue: 3 Pages: e1005507-e1005507

    • DOI

      10.1371/journal.ppat.1005507

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic potential of interleukin-27 against cancers in preclinical mouse models.2015

    • Author(s)
      Mizoguchi, I., Chiba, Y., Furusawa, J., Xu, M., Tsunoda, R., Higuchi, K., and Yoshimoto,
    • Journal Title

      Oncoimmunology

      Volume: 4(10) Issue: 10 Pages: e1042200-e1042200

    • DOI

      10.1080/2162402x.2015.1042200

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Potential clinical application of interleukin-27 as an antitumor agent.2015

    • Author(s)
      Yoshimoto, T., Chiba, Y., Furusawa, J., Xu, M., Tsunoda, R., Higuchi, K., and Mizoguchi, I.
    • Journal Title

      Cancer Sci.

      Volume: 106(9) Issue: 9 Pages: 1103-1110

    • DOI

      10.1111/cas.12731

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] A novel antitumor activity of IL-27 by promoting the differentiation of HSCs to antitumorigenic M1-like macrophages in tumor-bearing mice.2017

    • Author(s)
      Chiba, Y., Ohashi, M., Hasegawa, H., Xu, M., Owaki, T., Mizoguchi, I., and Yoshimoto, T.
    • Organizer
      The 2nd International Conference on Cytokine Signaling in Cancer
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel role for Epstein-Barr virus-induced gene 3 to augment IL-23 receptor α protein expression through a lectin chaperone calnexin.2017

    • Author(s)
      Mizoguchi, I., Ohashi, M., Hasegawa, H., Chiba, Y., Xu, M., and Yoshimoto, T.
    • Organizer
      第46回日本免疫学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Prediction of chemical respiratory and contact sensitizers by OX40L expression in dendritic cells using a novel 3D co-culture system.2017

    • Author(s)
      Ohashi, M., Mizoguchi, I., Chiba, Y., Hasegawa, H., Xu, M., and Yoshimoto, T.
    • Organizer
      第46回日本免疫学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IL-27 induces antitumor activity by promoting differentiation of HSCs to M1-like antitumorigenic macrophages and their mobiliziation into tumor.2016

    • Author(s)
      Chiba, Y., Mizoguchi, I., Hasegawa, H., Ohashi, M., C., Xu, M., and Yoshimoto, T.
    • Organizer
      第45回日本免疫学会総会・学術集会
    • Place of Presentation
      沖縄
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Promotion of expansion and differentiation of hematopoietic stem cells by IL-27 into myeloid progenitors to control infection in emergency myelopoiesis.2016

    • Author(s)
      Yoshimoto, T., Furusawa, J., Chiba, Y., Xu, M., Hasegawa, H., Nakae, S., Kobayashi, F., Yoshida, H., and Mizoguchi, I. Ohashi, M., Hasegawa, H., and Mizoguchi, I.
    • Organizer
      Symposium, 16th International Congress of Immunology
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of a novel in vitro evaluation system for the prediction of respiratory sensitizing potential of chemicals.2016

    • Author(s)
      Yoshimoto, T., Ohashi, M., Hasegawa, H., Chiba, Y., Xu, M., and Mizoguchi, I.
    • Organizer
      ICCA-LRI and NIHS Workshop
    • Place of Presentation
      Awaji Island
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 化学物質の呼吸器感作性in vitro評価法の開発2015

    • Author(s)
      善本隆之、千葉佑規乃、角田廉、徐明利、溝口出
    • Organizer
      第28回日本動物実験代替法学会
    • Place of Presentation
      横浜
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Binding of Epstein-Barr virus-induced gene 3 to calnexin enhances its chaperone activity and augments interleukin-23 receptor expression, leading to development of colitis.2015

    • Author(s)
      Mizoguchi, I., Chiba, Y., Xu, M., and Yoshimoto, T.
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 化学物質の呼吸器感作性in vitro評価法の開発2015

    • Author(s)
      溝口出、千葉佑規乃、角田廉、徐明利、善本隆之
    • Organizer
      第3期LRI研究報告会
    • Place of Presentation
      東京
    • Year and Date
      2015-08-28
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-16  

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