A novel regulatory role of IgG Fc receptor IIB in Flt3L-mediated dendritic cell development

• Project/Area Number: 19591181
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Juntendo University
• Principal Investigator: HIROSE Sachiko Juntendo University, 医学部, 准教授 (00127127)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Hiroyuki 桐蔭横浜大学, 医用工学部, 教授 (60189313)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 樹上細胞 / Fc・RIIB / Flt3 / SLE / 樹状細胞 / FcγRIIB / Akt

Research Abstract

Fms-like tyrosine kinase receptor 3 ligand (Flt3L)は前駆細胞を樹状細胞に分化させる増殖分化因子である。我々は今回、Fc・RIIB欠損マウスでは、抹消にCD11c+CD11b+CD8-の形質を持つmyeloid系樹状細胞が、正常マウスに比較して有意に増加していることを発見した。Flt3Lを添加した骨髄細胞培養系で解析した結果、Fc・RIIB欠損マウスの骨髄細胞培養では正常マウスに比較して、有意に多くの樹状細胞が得られた。その原因は、Flt3Lによる増殖能の亢進ではなく、アポトーシス抵抗性の亢進によることが示された。従って、Fc・RIIB分子には、Flt3Lによる樹状細胞分化過程において、アポトーシスを亢進することで増殖抑制に働くという、今まで知られていなかった機能が存在する可能性が示された。

Research Products

• [Journal Article] Fc・R-dependent expansion of a hyperactive monocyte subset in lupus-prone mice (2009)
  • Author(s): Santiago-Raber M-L, Amano H, Amano E, Baudino L, Otani M, Lin Q, Nimmerjahn F, Sjef Verbeek J, Ravetch JV, Takasaki Y, Hirose S, and Izui S
  • Journal Title: Arthritis Rheum (in press)
  • Peer Reviewed
• [Journal Article] Ankylosing enthesitis associated with up-regulated IFN- and IL-17 production in (BXSB x NZB) F1 male mice ; a new mouse model (2009)
  • Author(s): Abe Y, Ohtsuji M, Ohtsuji N, Lin Q, Tsurui H, Nakae S, Shirai T, Sudo K, and Hirose S
  • Journal Title: Mod. Rheum (in press)
  • Peer Reviewed
• [Journal Article] 自己免疫の発症とFcgレセプター臨床免疫・アレルギー科 (2009)
  • Author(s): 広瀬幸子、林青順
  • Journal Title: 科学評論社 (印刷中)
• [Journal Article] Centromeric interval of chromosome 4 derived from C57BL/6 mice accelerates type 1 diabetes in NOD. CD72^b congenic mice (2009)
  • Author(s): Hou R, Ohtsuji M, Ohtsuji N , Zhang L, Adachi T, Hirose S, Tsubata. T
  • Journal Title: Biochem. Biophys. Res. Commun 380 Pages: 193-197
  • Peer Reviewed
• [Journal Article] Aberrant genetic control of invariant TCR-bearing NKT cell function in New Zealand mouse strains : possible involvement in SLE pathogenesis (2008)
  • Author(s): Tsukamoto H, Ohtsuji M, Shiroiwa W, Lin Q, Nakamura K, Tsurui H, Jiang Y, Sudo K, Nishimura H, Shirai T, and Hirose S
  • Journal Title: J. Immunol 180 Pages: 4530-4539
  • Peer Reviewed
• [Journal Article] Delta-like 1 is essential for the maintenance of marginal zone B cells in normal mice but not in autoimmune mice (2008)
  • Author(s): Moriyama Y, Sekine C, Koyanagi A, Koyama N, Ogata H, Chiba S, Hirose S, Okumura K, and Yagita H
  • Journal Title: Int. Immunol 20 Pages: 763-773
  • NAID: 10021241547
  • Peer Reviewed
• [Journal Article] Jorgensen, TN, Tucker RM, Roark CL, Kotzin BL, Evans LH, and Izui S. Dissection of genetic mechanisms governing the expression of serum retroviral gp70 implicated in murine lupus nephritis (2008)
  • Author(s): Baudino L, Yoshinobu K, Morito N, Kikuchi S, Fossati-Jimack L, Morley BJ, Vyse TJ, Hirose S
  • Journal Title: J. Immunol 181 Pages: 2846-2854
  • Peer Reviewed
• [Journal Article] Splenic phagocytes promotes to nucleosomes in (NZB x NZW) F1 mice (2008)
  • Author(s): Okamoto A, Fujio K, van Rooijen N, Tsuno NH, Takahashi T, Tsurui H, Hirose S, Elkon KB, and Yamamoto K
  • Journal Title: J. Immunol 181 Pages: 5264-5271
  • Peer Reviewed
• [Journal Article] Aberrant genetic control of invariant TCR-bearing NKT cell function in New Zealand mouse strains : possible involvement in SLE pathogenesis. (2008)
  • Author(s): Tsukamoto H, et al.
  • Journal Title: J. Immunol. 180 Pages: 4530-4539
  • Peer Reviewed
• [Journal Article] Delta-like I is essential for the maintenance of marginal zone B cells in normal mice but not in autoimmune mice. (2008)
  • Author(s): Moroyama Y, et al.
  • Journal Title: Int. Immunol. 20 Pages: 763-773
  • Peer Reviewed
• [Journal Article] Dissection of genetic mechanisms governing the expression of serum retroviralgp70 implicated in murine lupus nephritis. (2008)
  • Author(s): Baudino L, et al.
  • Journal Title: J. Immunol. 181 Pages: 2846-2854
  • Peer Reviewed
• [Journal Article] Splenic phagocytes promotes to nucleosomes in(NZB x NZW)F1 mice. (2008)
  • Author(s): Okamoto A, et al.
  • Journal Title: J. Immunol. 181 Pages: 5264-5271
  • Peer Reviewed
• [Journal Article] Aberrant genetic control of invariant TCR-bearing NKT cell function in New Zealand mouse strains:possible involvement in SLE pathogenesis (2008)
  • Author(s): Tsukamoto K, et. al.
  • Journal Title: J.Immunol 180
  • Peer Reviewed
• [Journal Article] IL-4R・polymorphism in regulation of IL-4 synthesis by T cells : implication in susceptibility to a subset of murine lupus (2007)
  • Author(s): Shiroiwa W, Tsukamoto K, Ohtsuji M, Lin Q, Ida A, Kodera S, Ohtsuji N, Nakamura K, Tsurui H, Kinoshita K, Nishimura H, Shirai T, and Hirose S
  • Journal Title: Int. Immunol 19 Pages: 175-183
  • Peer Reviewed
• [Journal Article] CD3 and IgG Fc receptor regulate cerebellar functions (2007)
  • Author(s): Nakamura K, Hirai H, Torashima T, Miyazaki T, Tsurui H, Xiu Y, Ohtsuji M, Qing Shun Lin Q, Tsukamoto K, Nishimura H, Ono M, Watanabe M and Hirose S
  • Journal Title: Mol. Cell. Biol 27 Pages: 5128-5134
  • Peer Reviewed
• [Journal Article] 全身性自己免疫疾患とFc・レセプターによる免疫反応の正と負の調節 (2007)
  • Author(s): 林青順、広瀬幸子
  • Journal Title: 臨床免疫・アレルギー科科学評論社 47 Pages: 545-550
• [Journal Article] CD3 and IgG Fc receptor regulate cerebellar functions (2007)
  • Author(s): Nakamura K, et. al.
  • Journal Title: Mol.Cell.Biol 27 Pages: 5127-5134
  • Peer Reviewed
• [Journal Article] 全身性自己免疫疾患とFcγレセプターによる免疫反応の正と負の調節 (2007)
  • Author(s): 林 青順、広瀬 幸子
  • Journal Title: 臨床免疫・アレルギー科 47 Pages: 545-550
• [Presentation] FcgR-dependent expansion of Gr-1- monocyte subset in lupus prone mice (2008)
  • Author(s): Amano H, Amano E, Lin Q. Ando S, Nishimura H, Moromoto S, Hirose S, Takasaki Y
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] (NZW x BXSB) F1マウスにおけるFcgr2bプロモーター領域の多型性の影響 (2008)
  • Author(s): Lin Q、Tsurui H, Ohtsuji M, Amano H、Nishimura H, Shirai T, Hirose S
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] 抑制型IgG FcレセプターによるB細胞分化の制御 (2008)
  • Author(s): 林青順、天野浩文、天野恵理、白井俊一、広瀬幸子
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
• [Presentation] SLE動物モデルにおけるT細胞の活性化 (2008)
  • Author(s): 藤尾圭志、岡本明子、鶴井博理、広瀬幸子、山本一彦
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
• [Presentation] BXSBマウスの末梢血単球増加におけるFcγレセプターの役割 (2008)
  • Author(s): 天野浩文、天野恵理、安藤誠一郎、仲野総一郎、森本真司、戸叶嘉明、林青順、西村裕之、広瀬幸子、高崎芳成
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
• [Presentation] (NZW x BXSB)F1マウスにおけるFcgr2bプロモーター領域の多型性の影響 (2008)
  • Author(s): Lin Q, et al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] SLE動物モデルにおけるT細胞の活性化 (2008)
  • Author(s): 藤尾 圭志, 他
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] BXSBマウスの末梢血単球増加におけるFc γレセプターの役割 (2008)
  • Author(s): 天野 浩文, 他
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Protection from autoimmune disease by restoration of impaired FcgRIIB expression (2007)
  • Author(s): Lin Q, Ohtsuji M, Amano H, Amano E, Tsurui H, Nishimura H, Shirai T, Hirose S
  • Organizer: 第37回日本免疫学会・学術集会
  • Place of Presentation: 東京
• [Presentation] Association of NKT cell function with systemic lupus erythematosus (2007)
  • Author(s): Hirose S, Tsukamoto K, Ohtsuj M, Lin Q, Tsurui H, Nishimura H, Shirai T
  • Organizer: 第37回日本免疫学会・学術集会
  • Place of Presentation: 東京
• [Presentation] BXSBマウスの末梢血単核球増加におけるIgGFcレセプターの役割 (2007)
  • Author(s): 天野浩文、天野恵理、安藤誠一郎、仲野総一郎、森本真司、戸叶嘉明、林青順、西村裕之、広瀬幸子、高崎芳成
  • Organizer: 第37回日本免疫学会・学術集会
  • Place of Presentation: 東京
• [Presentation] 末梢性の免疫寛容誘導における抑制性Fc受容体FcgRIIBの役割 (2007)
  • Author(s): 軸丸由梨、藤井琢磨、池田賢一、大木麻紀子、吉澤侑也、小寺洋、広瀬幸子、白井俊一、西村裕之
  • Organizer: 第37回日本免疫学会・学術集会
  • Place of Presentation: 東京