Role of NF-kB-inducing kinase (NIK) in the differentiation of myeloid-derived suppressor cells

• Project/Area Number: 26430120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kitasato University
• Principal Investigator: Eshima Koji 北里大学, 医学部, 准教授 (30327324)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 骨髄由来抑制性細胞 / 骨髄由来免疫抑制性細胞 / NF-kB-inducing kinase / 免疫抑制

Outline of Final Research Achievements

Myeloid-derived suppressor cells (MDSC) are known to inhibit immune responses against tumors or in chronic infections, although their developmental mechanisms have remained unclear. In this study, we noticed that MDSC-like cells are spontaneously accumulated in alymphoplasia, the mice bearing a mutation in NF-kB-inducing kinase. We analyzed the phenotypes and function of these cells comparing them with those of tumor-induced MDSCs, and following results were obtained. (1) MDSC-like cells in aly mice were divided into three populations in terms of their expression of Ly6C and Ly6G. (2) All of these three population exhibited the ability to suppress T cell proliferation at similar level as tumor-induced MDSCs. (3) These populations were not observed in aly mice lacking mature lymphocytes. These results collectively indicated that lack of functional NIK may lead to the development of MDSC, and that the development of (subsets of) MDSC may be dependent on the function of lymphocytes.

Research Products

• [Journal Article] Thromboxane A synthase enhances blood flow recovery from hindlimb ischemia. (2016)
  • Author(s): Amano H, Nakamura M, Ito Y, Kakutani H, Eshima K, Kitasato H, Narumiya S, Majima M.
  • Journal Title: J Surg Res. Volume: 204 Issue: 1 Pages: 153-163
  • DOI: 10.1016/j.jss.2016.04.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] BLT1 signalling protects the liver against acetaminophen hepatotoxicity by preventing excessive accumulation of hepatic neutrophils (2016)
  • Author(s): Kojo, K., Ito, Y., Eshima, K., Nishizawa, N., Ohkubo, H., Yokomizo, T., Shimizu, T., Watanabe, M.,Majima, M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 29650-29650
  • DOI: 10.1038/srep29650
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitory function of NKT cells during early induction phase of nickel allergy. (2016)
  • Author(s): Hironori Okuno, Masashi Satoh, Emiko Takeuchi, Koji Eshima, Masazumi Terashima, Jun Komotori, Sonoko Habu, Hidekazu Tamauchi, Kazuya Iwabuchi.
  • Journal Title: Immunobiology Volume: in press Issue: 7 Pages: 833-838
  • DOI: 10.1016/j.imbio.2016.01.012
  • Peer Reviewed / Open Access
• [Journal Article] The role of vascular endothelial growth factor receptor-1 signaling in compensatory contralateral lung growth following unilateral pneumonectomy. (2015)
  • Author(s): Matsui Y, Amano H, Ito Y, Eshima K, Tamaki H, Ogawa F, Iyoda A, Shibuya M, Kumagai Y, Satoh Y, Majima M.
  • Journal Title: Laboratory Investigation Volume: 95 Issue: 5 Pages: 456-468
  • DOI: 10.1038/labinvest.2014.159
  • Peer Reviewed
• [Journal Article] Thromboxane A2 induces blood flow recovery via platelet adhesion to ischaemic regions. (2015)
  • Author(s): Amano H, Ito Y, Eshima K, Kato S, Ogawa F, Hosono K, Oba K, Tamaki H, Sakagami H, Shibuya M, Narumiya S, Majima M.
  • Journal Title: Cardiovasc Res. Volume: 107 Issue: 4 Pages: 509-521
  • DOI: 10.1093/cvr/cvv139
  • Peer Reviewed / Open Access
• [Journal Article] Differential dependence on nuclear factor-κB-inducing kinase among natural killer T-cell subsets in their development. (2015)
  • Author(s): Noma H, Eshima K, Satoh M, Iwabuchi K
  • Journal Title: Immunology Volume: 146 Issue: 1 Pages: 89-99
  • DOI: 10.1111/imm.12484
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from Ischemia. (2015)
  • Author(s): Amano H, Kato S, Ito Y, Eshima K, Ogawa F, Takahashi R, Sekiguchi K, Tamaki H, Sakagami H, Shibuya M, Majima M.
  • Journal Title: PLoS One Volume: 10
  • Peer Reviewed / Open Access
• [Presentation] Spontaneous accumulation of myeloid-derived suppressor cell (MDSC)-like CD11b+/Gr-1+ cells in the periphery of NF-κB-inducing kinase (NIK) mutant mice (2017)
  • Author(s): 大橋千尋，江島耕二，岩渕和也
  • Organizer: 第46回日本免疫学会総会・学術集会
• [Presentation] The effects of transgenic expression of a T-box molecule, Eomesodermin, in naive T cells on their activation and exhaustion status. (2016)
  • Author(s): Koji Eshima, Haruka Noma, Kana Misawa, Kazuya Iwabuchi
  • Organizer: 第15回国際免疫学会議
  • Place of Presentation: メルボルン（オーストラリア）
  • Int'l Joint Research
• [Presentation] Transgenic expression of a T-box molecule, Eomesodermin, in naive T cells induced expression of some activation/exhaustion markers without conferring functionality. (2016)
  • Author(s): 江島耕二，三澤佳奈，岩渕和也
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
• [Presentation] Functional analyses of peripheral T cells and of cortical thymic epithelial cells in immune-compromized, alymphoplasia mice. (2016)
  • Author(s): 三澤佳奈，江島耕二，岩渕和也
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
• [Presentation] On the in vivo effects of enforced expression of eomesodermin, a T-box family molecule, in naïve T cells on their differentiation and function. (2015)
  • Author(s): 江島耕二，野間春香，岩渕和也
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-19
• [Presentation] Differential dependence on NF-κB-inducing kinase among NKT cell subsets in their development. (2015)
  • Author(s): 野間春香，江島耕二，佐藤雅，岩渕和也
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-19
• [Presentation] 正常なマウス胸腺皮質上皮細胞維持におけるNF-kB-inducing kinase (NIK) の関与 (2015)
  • Author(s): 江島耕二，野間春香，岩渕和也
  • Organizer: 第34回日本胸腺研究会
  • Place of Presentation: ユニコムプラザさがみはら（神奈川県相模原市）
  • Year and Date: 2015-02-07
• [Presentation] Subtype-dependent requirement of NF-kB-inducing kinase in NKT cell differentiation. (2014)
  • Author(s): 野間春香，江島耕二，佐藤雅，岩渕和也
  • Organizer: 第43回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-12-10
• [Remarks] 北里大学医学部免疫学単位
  • URL: http://www.med.kitasato-u.ac.jp/immunology/index.html
• [Remarks] 北里大学医学部免疫学
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html
• [Remarks] 北里大学医学部免疫学単位
  • URL: http://web.med.kitasato-u.ac.jp/edures/immunol.html