Novel immune regulation by PirB-related multiple ligands

• Project/Area Number: 24249016
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: TAKAI Toshiyuki 東北大学, 加齢医学研究所, 教授 (20187917)
• Co-Investigator(Renkei-kenkyūsha): INUI Masanori 東北大学, 加齢医学研究所, 講師 (80443985) ; ENDO Shota 東北大学, 加齢医学研究所, 助教 (70466580)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥46,020,000 (Direct Cost: ¥35,400,000、Indirect Cost: ¥10,620,000); Fiscal Year 2014: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000); Fiscal Year 2013: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000); Fiscal Year 2012: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
• Keywords: 免疫制御 / 免疫抑制 / 免疫受容体 / 自然免疫 / アレルギー / 自己免疫疾患 / B細胞分化 / 抗体産生 / 制御受容体 / 自己抗体 / PirB / B細胞

Outline of Final Research Achievements

We have attempted to elucidate a whole spectrum of PirB (or human LILRB)-mediated immune regulation through its binding to the multiple ligands such as Nogo and MHC class I molecules, and to develop novel therapeutic strategies against immune disorders such as allergy and autoimmune diseases. We have found that Nogo is preferentially localized to endoplasmic reticulum and regulates TLR9-mediated immune activation via interacting with GRAMD4 but not PirB. Also, we have characterized a human novel B-lineage cell subset, CD43+ B cells, as an intermittent pre-plasmablastic population but not human B1-like cells, being positioned between memory B cells and plasmablasts in terms of its surface LILRB expression, antibody and cytokine secretion, and transcriptional factor expression profiles.

Research Products

• [Journal Article] Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fcγ receptors. (2015)
  • Author(s): Inui M, Tazawa K, Kishi Y, Takai T.
  • Journal Title: BMC Immunol. Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Endoplasmic protein Nogo-B (RTN4-B) interacts with GRAMD4 and regulates TLR9-mediated innate immune responses. (2015)
  • Author(s): Kimura T, Endo S, Inui M, Saitoh S-i, Miyake K, Takai T.
  • Journal Title: J. Immunol. Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human CD43+ B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally in healthy individuals. (2015)
  • Author(s): Inui M, Hirota S, Hirano K, Fujii H, Sugahara-Tobinai A, Ishii T, Harigae H, Takai T.
  • Journal Title: Int Immunol. Volume: pii
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immune complexes regulate bone metabolism through FcRγ signaling. (2015)
  • Author(s): Nehishi–Koga T, Gober HJ, Sumiya E, Komatsu N, Okamoto K, Sawa S, Suematsu S, Suda T, Sato K, Takai T, Takayanagi H.
  • Journal Title: Nat Commun Volume: in press
  • Peer Reviewed
• [Journal Article] A DAP12-Dependent Signal Promotes Pro-Inflammatory Polarization in Microglia Following Nerve Injury and Exacerbates Degeneration of Injured Neurons. (2015)
  • Author(s): Kobayashi M, Konishi H, Takai T, Kiyama H.
  • Journal Title: Glia Volume: in press
  • Peer Reviewed
• [Journal Article] Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. (2015)
  • Author(s): Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, Fukui R, Shimozato T, Yamamoto K, Shibata T, Sano S, Sugahara-Tobinai A, Takai T, Ohto U, Shimizu T, Saitoh S, Miyake K.
  • Journal Title: Nat Commun Volume: 6 Pages: 6119-6119
  • Peer Reviewed
• [Journal Article] Dichotomy in the FcγRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis. (2014)
  • Author(s): Kanari Y, Sugahara–Tobinai A, Takahashi H, Inui M, Nakamura A, Hirose S, Takai T.
  • Journal Title: BMC Immunol. Volume: 15 Pages: 1-13
  • DOI: 10.1186/s12865-014-0047-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gp49B-mediated negative regulation of antibody production by memory and marginal zone B cells. (2014)
  • Author(s): Fukao S, Haniuda K, Nojima T, Takai T, Kitamura D.
  • Journal Title: The Journal of Immunology Volume: 193 Pages: 635-644
  • DOI: 10.4049/jimmunol.1302772
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An ITAM-Syk-CARD9 signaling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells (2014)
  • Author(s): Yasukawa. S., Miyazaki, Y., Yoshii, C., Nakaya, M., Ozaki, N., Toda, S., Kuroda, E., Ishibashi, K., Yasuda, T., Natsuaki, Y., Mi-ichi, F., Iizasa, E., Nakahara, T., Yamazaki, M., Kabashima, K., Iwakura, Y., Takai, T., Saito, T., Kurosaki, T., Malissen, B., Ohno, N., Furue, M., Yoshida, H., and Hara, H
  • Journal Title: Nat Commun. Volume: 5 Pages: 3755-3755
  • DOI: 10.1038/ncomms4755
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TREM-1 regulates macrophage polarization in ureteral obstruction. (2014)
  • Author(s): Lo TH, Tseng KY, Tsao WS, Yang CY, Hsieh SL, Chiu AW, Takai T, Mak TW, Tarng DC, Chen NJ.
  • Journal Title: Kidney Int. Volume: 86(6) Pages: 1174-1186
  • DOI: 10.1038/ki.2014.205
  • Peer Reviewed
• [Journal Article] Role of TREM1-Dap12 in renal inflammation during obstructive nephropathy. (2013)
  • Author(s): Stroo I, Tammarro A, Rampanelli E, Blank F, Butter L, Claessen N, Takai T, Colonna M, Leemans J, Florquin S, Dessing MC.
  • Journal Title: PLOS ONE Volume: in press
  • Peer Reviewed
• [Journal Article] Environmental factors determine DAP12 deficiency to either enhance or suppress immunopathogenic processes. (2013)
  • Author(s): Montalvo V, Quigley L, Vistica BP, Boelte KC, Nugent LF, Takai T, McVicar DW, Gery I.
  • Journal Title: lmmunology Volume: Dec;140(4) Pages: 475-482
  • DOI: 10.1111/imm.12158
  • Peer Reviewed
• [Journal Article] IgG and IgE collaboratively accelerate expulsion of Strongyloides venezuelensis in a primary infection. (2013)
  • Author(s): Makoto Matsumoto, Yuki Sasaki, Koubun Yasuda, Toshiyuki Takai, Masamichi Muramatsu, Tomohiro Yoshimoto, Kenji Nakanishi.
  • Journal Title: lnfect. lmmun Volume: Vol.81、No.7 Pages: 2518-2527
  • DOI: 10.1128/iai.00285-13
  • Peer Reviewed
• [Journal Article] The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis. (2013)
  • Author(s): Kuroki Kら
  • Journal Title: Hum lmmunol Volume: 74 Pages: 433-438
  • DOI: 10.1016/j.humimm.2012.11.060
  • NAID: 120005297913
  • Peer Reviewed
• [Journal Article] Phenotype conversion from rheumatoid arthritis to systemic lupus erythematosus by introduction of Yaa mutation into FcgRIIB-deficient C57BL/6 (2013)
  • Author(s): Kawano S, Lin Q, Amano H, Kaneko T, Nishikawa K, Tsurui H, Tada N, Nishimura H,Takai T, Shirai T, Takasaki Y and Hirose S
  • Journal Title: Eur J Immunol. Volume: 43 Pages: 770-778
  • DOI: 10.1002/eji.201243057
  • Peer Reviewed
• [Journal Article] Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro (2012)
  • Author(s): Tanaka J
  • Journal Title: Open J. lmmunol Volume: vol. 2 Pages: 149-160
  • DOI: 10.4236/oji.2012.24019
  • Peer Reviewed
• [Journal Article] Inhibitory receptor PIR-B is exploited by Staphylococcus aureus for virulence (2012)
  • Author(s): Nakayama M, Kurokawa K, Nakamura K, Lee BL, Sekimizu K, Kubagawa H, Hiramatsu K, Yagita H, Okumura K, Takai T, Underhill DM, Aderem A, Ogasawara K.
  • Journal Title: J. lmmunol Volume: 189 Pages: 5903-11
  • DOI: 10.4049/jimmunol.1201940
  • Peer Reviewed
• [Journal Article] Regulation of plasmacytoid dendritic cell responses by PIR-B. (2012)
  • Author(s): MitsuhashiY,NakamuraA,EndoS,TakedaK,Yabe-WadaT,NukiwaT,TakaiT(correspondenceauthor)
  • Journal Title: Blood Volume: 120 Pages: 3256-3259
  • DOI: 10.1182/blood-2012-03-419093
  • Peer Reviewed
• [Journal Article] Deletion of cognate CD8 T-cells by immature dendritic cells: a novel role for perforin, Granzyme A, TREM-1 and TLR7 (2012)
  • Author(s): Zangi L
  • Journal Title: Blood Volume: 120 Pages: 1647-57
  • DOI: 10.1182/blood-2012-02-410803
  • Peer Reviewed
• [Journal Article] Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells. (2012)
  • Author(s): Wong WF, Tazawa R, （15名略）Nakata K, Takai T, Satake M.
  • Journal Title: J. Immunol Volume: 188(11) Pages: 5408-20
  • DOI: 10.4049/jimmunol.1102991
  • Peer Reviewed
• [Presentation] 「疾患制御におけるIgGとFcレセプター」 (2015)
  • Author(s): 髙井俊行
  • Organizer: 救急集中治療セミナー
  • Place of Presentation: 東京女子医大
  • Year and Date: 2015-03-04
  • Invited
• [Presentation] 「Fc受容体による自己免疫の制御」 (2014)
  • Author(s): 髙井俊行
  • Organizer: 第79回インターフェロン・サイトカイン学会：シンポジウム
  • Place of Presentation: 北海道大学
  • Year and Date: 2014-06-19
  • Invited
• [Presentation] Negative Regulation of Autoantibody Production by a B Cell Inhibitory Receptor, FcγRIIB
  • Author(s): Toshiyuki Takai
  • Organizer: Centennial of Hashimoto Disease Symposium
  • Place of Presentation: Fukuoka
  • Invited
• [Remarks] 遺伝子導入研究分野ホームページ
• [Remarks] 遺伝子導入研究分野ホームページ
  • URL: http://www2.idac.tohoku.ac.jp/dep/expimmu/