Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fcg receptors.

• Project/Area Number: 26670230
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tohoku University
• Principal Investigator: TAKAI Toshiyuki 東北大学, 加齢医学研究所, 教授 (20187917)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 抗炎症 / Fcレセプター / 抑制シグナル / IgG / IL-10 / ヒト単球 / サイトカイン / Fc受容体 / 血小板

Outline of Final Research Achievements

Augmented production of an immunoregulatory cytokine IL-10 with a concomitant reduction of proinflammatory cytokines in macrophages in vitro is attained by doubly stimulating the cells with a TLR ligand and IgG immune complexes, a response known as that of regulatory macrophages. However, it has not been explored sufficiently how such a regulatory response occurs in more physiologic settings. We showed that IgG-opsonized platelets convert human peripheral blood circulating monocytes to IL-10-producing regulatory monocytes in vitro and in vivo. This novel way of enhancing IL-10 was mediated by activating-type Fc receptor FcγRIIA. A therapeutic preparation of human polyclonal IgG (or IVIG) was found to react to platelets via the Fab portion, thereby converting circulating monocytes to regulatory cells. These findings indicate that the IgG-bound platelet-induced conversion provides a novel mechanism for homeostatic generation of regulatory monocytes.

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: 16 Issue: 1 Pages: 20-20
  • DOI: 10.1186/s12865-015-0086-z
  • Peer Reviewed / Open Access
• [Journal Article] Platelets convert peripheral blood circulating monocytes to regulatory cells via immunoglobulin G and activating-type Fc 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: 47-47
  • 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: J Immunol. Volume: 193 Issue: 2 Pages: 635-644
  • DOI: 10.4049/jimmunol.1302772
  • Peer Reviewed / Open Access
• [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: Nature Comm Volume: 5 Issue: 1 Pages: 3755-3755
  • DOI: 10.1038/ncomms4755
  • Peer Reviewed / Open Access
• [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) Issue: 6 Pages: 1174-1186
  • DOI: 10.1038/ki.2014.205
  • 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
• [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/