The role of phosphatase regulatory subunit G5PR in the differentiation of autoantibody producing cells from B1 cells

• Project/Area Number: 15K09532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nara Medical University
• Principal Investigator: Masahiro Kitabatake 奈良県立医科大学, 医学部, 講師 (60457588)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自己抗体 / G5PR / JNK / 形質細胞分化 / 胚中心 / B1細胞

Outline of Final Research Achievements

Self-reactive IgG autoantibodies are hallmark of autoimmune diseases, and often cause tissue damage. Although B1 cells, which naturally produce self-reactive IgM, are thought to be the precursor cells of IgG autoantibody-secreting cells in autoimmune diseases, the underlying mechanisms of differentiation process remain poorly understood. Here, we showed that activated B1 cells from autoimmune-prone mice migrated into germinal center of secondary lymphoid organ and then underwent a process of class switch recombination to IgG and differentiation into antibody-producing plasma cells. In addition, stimulation of TLR ligand and various cytokines in the germinal center like environment induced G5PR expression in B1 cells, leading to JNK suppression and plasma cell differentiation. These results suggest that regulation of G5PR/JNK pathway might be a potential therapeutic target for autoimmune diseases.

Research Products

• [Journal Article] Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease (2017)
  • Author(s): Yoko Matsumura, Masahiro Kitabatake, Noriko Ouji-Sageshima, Satsuki Yasui, Naoko Mochida, Ryuichi Nakano, Kei Kasahara, Koichi Tomoda, Hisakazu Yano, Shin-ichi Kayano, Toshihiro Ito
  • Journal Title: PLoS One Volume: 12 Issue: 8 Pages: e0183489-e0183489
  • DOI: 10.1371/journal.pone.0183489
  • Peer Reviewed / Open Access
• [Journal Article] Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development (2017)
  • Author(s): Yoshiro Kai, Koichi Tomoda, Hiroyuki Yoneyama, Masahiro Kitabatake, Atsuhiro Nakamura, Toshihiro Ito, Masanori Yoshikawa, and Hiroshi Kimura.
  • Journal Title: Molecular Therapy - Nucleic Acids Volume: 6 Pages: 163-172
  • DOI: 10.1016/j.omtn.2016.12.008
  • Peer Reviewed / Open Access
• [Journal Article] Sensitization with vaccinia virus harboring hemagglutinin recovers the immune potential against highly pathogenic H5N1 influenza virus in non-human primates (2016)
  • Author(s): Fumihiko Yasui, Yasushi Itoh, Ai Ikejiri, Masahiro Kitabatake, Nobuo Sakaguchi, Keisuke Munekata, Shintaro Shichinohe, Yukiko Hayashi, Hirohito Ishigaki, Misako Nakayama, Yoshihiro Sakoda, Hiroshi Kida, Kazumasa Ogasawara, *Michinori Kohara
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 37915-37915
  • DOI: 10.1038/srep37915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] CD8+ T cells play a critical role for the murine model of immune reconstitution inflammatory syndrome. (2017)
  • Author(s): Masahiro Kitabatake, Mitsuru Konishi, Yoko Matsumura, Noriko Ouji-Sageshima, Natsuko Imakita, and Toshihiro Ito.
  • Organizer: 第46回日本免疫学会総会・学術集会
• [Presentation] Critical role of interferon secreted CD8+ T cells in Mycobacterium avium complex infection in immune reconstitution inflammatory syndrome (IRIS) model. (2017)
  • Author(s): Masahiro Kitabatake, Mitsuru Konishi, Yoko Matsumura, Noriko Ouji-Sageshima, Natsuko Imakita, and Toshihiro Ito.
  • Organizer: Cytokine2017
  • Int'l Joint Research
• [Presentation] Cigarette smoke attenuated colon inflammation in ulcerative colitis model (2017)
  • Author(s): Masahiro KITABATAKE, Koichi TOMODA, Kaoru KUBO, and Toshihiro ITO.
  • Organizer: Immunology2017
  • Int'l Joint Research
• [Presentation] Establishment of immune reconstitution inflammatory syndrome (IRIS) model and critical role of CD8+ T cells (2016)
  • Author(s): Masahiro Kitabatake, Mitsuru Konishi, Yoko Matsumura, Noriko Ouji-Sageshima, Natsuko Imakita, and Toshihiro Ito.
  • 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
• [Presentation] Highly pathogenic avian influenza A H5N1 virus causes severe symptoms due to insufficient interaction of dendritic cells with T cells (2015)
  • Author(s): Ai Ikejiri, Fumihiko Yasui, Yasushi Itoh, Masahiro Kitabatake, Nobuo Sakaguchi, Kazumasa Ogasawara, Michinori Kohara
  • 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
  • Year and Date: 2015-11-18