Identification of human regulatory B cells and their role in autoimmune diseases

• Project/Area Number: 24591450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyushu University
• Principal Investigator: NIIRO HIROAKI 九州大学, 大学病院, 准教授 (20380636)
• Co-Investigator(Kenkyū-buntansha): AKASHI Koichi 九州大学, 医学研究院, 教授 (80380385)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 自己免疫疾患 / B細胞 / 免疫学

Outline of Final Research Achievements

In the present study, we showed that IL-10-producing regulatory B cells (Bregs) are predominantly induced in human IgM-memory B cell subsets in the peripheral blood, and also showed that Blimp-1, a master regulator of plasma cell differentiation, plays a critical role in Breg induction. Patients with SLE, a prototypic autoimmune disease, exhibited defective Breg function mainly via impaired induction of Blimp-1.

Research Products

• [Journal Article] Increased Syk phosphorylation leads to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus. (2015)
  • Author(s): Iwata S, Yamaoka K, Niiro H, Jabbarzadeh-Tabrizi S, Wang SP, Kondo M, Yoshikawa M, Akashi K, Tanaka
  • Journal Title: Lupus Volume: 24 Pages: 695-704
  • Peer Reviewed
• [Journal Article] Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy (2014)
  • Author(s): Ishikawa K, Yoshida S, Nakao S, Nakama T, Kita T, Asato R, Sassa Y, Arita R, Miyazaki M, Enaida H, Oshima Y, Murakami N, Niiro H, Ono J, Matsuda A, Goto Y, Akashi K, Izuhara K, Kudo A, Kono T, Hafezi-Moghadam A, Ishibashi T.
  • Journal Title: FASEB J Volume: 28 Issue: 1 Pages: 131-142
  • DOI: 10.1096/fj.13-229740
  • Peer Reviewed / Open Access
• [Journal Article] Charateristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan. (2014)
  • Author(s): Ono N, Niiro H, Ueda A, Sawabe T, Nishizaka H, Furugo I, Yoshizawa S, Yoshizawa S, Tsukamoto H, Kiyohara C, Tada Y, Horiuchi
  • Journal Title: Rheumatol Int Volume: 35 Issue: 3 Pages: 555-559
  • DOI: 10.1007/s00296-014-3106-z
  • Peer Reviewed
• [Journal Article] Reduced carotid intima-media thickness in systemic lupus erythematosus patients treated with cyclosporine A. (2013)
  • Author(s): Oryoji K, Kiyohara C, Horiuchi T, Tsukamoto H, Niiro H, Shimoda T, Akashi K, Yanase T
  • Journal Title: Mod Rheumatol Volume: 24 Issue: 1 Pages: 86-92
  • DOI: 10.3109/14397595.2013.852838
  • Peer Reviewed
• [Journal Article] The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α. (2013)
  • Author(s): Ueda N, Tsukamoto H, Mitoma H, Ayano M, Tanaka A, Ohta S, Inoue Y, Arinobu Y, Niiro H, Akashi K, Horiuchi T.
  • Journal Title: Inflamm Bowel Dis. Volume: 19 Issue: 6 Pages: 1224-1231
  • DOI: 10.1097/mib.0b013e318280b169
  • Peer Reviewed
• [Journal Article] PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells. (2012)
  • Author(s): Yuki H
  • Journal Title: Blood Volume: 121 Issue: 6 Pages: 962-970
  • DOI: 10.1182/blood-2012-05-431429
  • Peer Reviewed
• [Journal Article] CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells (2012)
  • Author(s): Niiro H,…, Tsukamoto H, et al(16名中12番目)
  • Journal Title: Blood Volume: 119 Issue: 10 Pages: 2263-2273
  • DOI: 10.1182/blood-2011-04-351965
  • Peer Reviewed
• [Journal Article] Amplification of toll-like receptor-mediated signaling through Syk in human B activation. (2012)
  • Author(s): Iwata S, Yamaoka K, Niiro H, Nakano K, Wang SP, Akashi K, and Tanaka Y
  • Journal Title: J Allergy Clin Immunol Volume: 129 Issue: 6 Pages: 1594-1601
  • DOI: 10.1016/j.jaci.2012.03.014
  • Peer Reviewed
• [Journal Article] The role of natural killer (NK) and NK T cells in the loss of tolerance in murine primary biliary cirrhosis. (2012)
  • Author(s): Shimoda S, Tsuneyama K, et al.
  • Journal Title: Clin Exp Immunol. Volume: 168(3) Issue: 3 Pages: 279-84
  • DOI: 10.1111/j.1365-2249.2012.04581.x
  • Peer Reviewed
• [Journal Article] Serum progranulin levels are elevated in patients with systemic lupus erythematosus, reflecting disease activity. (2012)
  • Author(s): Tanaka A, Tsukamoto H, Mitoma H, Kiyohara C, Ueda N, Ayano M, Ohta SI, Inoue Y, Arinobu Y, Niiro H, Horiuchi T, and Akashi K
  • Journal Title: Arthritis Res Ther Volume: 14
  • Peer Reviewed
• [Presentation] Elucidation of melecular mechanisms of Breg induction in autoimmune diseases (2014)
  • Author(s): Shun-ichiro Ota, Hiroaki Niiro, Naoko Ueki, Yuri Hirosaki, Hirofumi Tsuzuki, Kumiko Noda, Siamak Jabbarzadeh-Tabrizi,Atsushi Tanaka, Hiroki Mitoma, Yojiro Arinobu, Mitsuteru Akahoshi, Hiroshi Tsukamoto, and Koichi Akashi.
  • Organizer: ACR annual meeting 2014
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2014-11-18
• [Presentation] エフェクターB細胞 (2014)
  • Author(s): 新納 宏昭
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] 関節リウマチ患者におけるトシリズマブの有効性および酸化ストレスマーカー変化量の検討 ―中間解析から得られた知見 - (W4-4) (2014)
  • Author(s): 新納宏昭、塚本浩、有信洋二郎、赤星光輝、木本泰孝、藤健太郎、押領司健介、井上靖、澤部琢哉、永野修司、西坂浩明、吉澤誠司、多田芳史、吉澤滋、大塚毅、上田章、中島衡、堀内孝彦、赤司浩一
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24
• [Presentation] 全身性エリテマトーデス患者におけるGranzyme B産生B細胞の役割 (W10-1) (2014)
  • Author(s): 植木尚子、新納宏昭、大田俊一郎、廣崎友里、野田久美子、上田尚靖、田中淳、綾野雅宏、上田彰、久本仁美、押領司大助、中川仁、中野翔太、木本泰孝、赤星光輝、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24
• [Presentation] 健常人ならびにSLE患者における制御性B細胞の誘導メカニズムの検討 (2014)
  • Author(s): 大田俊一郎、新納宏昭、植木尚子、廣崎友里、野田久美子、田中淳、綾野雅宏、上田彰、久本仁美、押領司大助、中川仁、中野翔太、上田尚靖、木本泰孝、赤星光輝、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24
• [Presentation] 健常人ならびにSLE患者B細胞におけるIRAK-M発現とその機能
  • Author(s): 新納宏昭、ジャバルザデータブリッジ シアマック、大田俊一郎、植木尚子、廣崎友里、野田久美子、上田尚靖、田中淳、上田彰、久本仁美、綾野雅宏、押領司大助、赤星光輝、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第57回日本リウマチ学会総会 学術集会
  • Place of Presentation: 京都
• [Presentation] 健常人ならびにSLEにおけるgranzyme B産生制御性B細胞の比較検討
  • Author(s): 植木尚子、新納宏昭、大田俊一郎、廣崎友里、ジャバルザデータブリッジ シアマック、野田久美子、上田尚靖、田中淳、綾野雅宏、上田彰、久本仁美、押領司大助、赤星光輝、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第57回日本リウマチ学会総会 学術集会
  • Place of Presentation: 京都
• [Presentation] 関節リウマチ患者と健常人におけるB細胞のRANKL発現の比較検討
  • Author(s): 廣崎友里、新納宏昭、大田俊一郎、植木尚子、綾野雅宏、赤星光輝、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第41回日本臨床免疫学会総会
  • Place of Presentation: 下関
• [Presentation] Cblアダプター分子CIN85によるB細胞機能制御とSLE患者B細胞における役割
  • Author(s): 新納宏昭、Siamak Jabbarzadeh-Tabrizi、大田俊一郎、植木尚子、野田久美子、上田尚靖、田中淳、上田彰、綾野雅宏、久本仁美、古川牧緒、井上靖、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第56回日本リウマチ学会総会•学術集会
  • Place of Presentation: 東京
• [Presentation] 抗BAFF抗体、TACI-Ig
  • Author(s): 新納宏昭
  • Organizer: 第56回日本リウマチ学会総会•学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 健常人ならびにSLE患者における制御性B細胞の比較検討
  • Author(s): 大田俊一郎、新納宏昭、植木尚子、Siamak Jabbarzadeh-Tabrizi、野田久美子、上田尚靖、田中淳、上田彰、久本仁美、綾野雅宏、古川牧緒、井上靖、有信洋二郎、塚本浩、堀内孝彦、赤司浩一
  • Organizer: 第56回日本リウマチ学会総会•学術集会
  • Place of Presentation: 東京
• [Remarks] 九州大学医学部 第一内科
  • URL: http://www.1nai.med.kyushu-u.ac.jp/professional/immunity02.php
• [Remarks] 九州大学医学部 第一内科
  • URL: http://www.1nai.med.kyushu-u.ac.jp/
• [Remarks] 九州大学医学研究院 病態修復内科
  • URL: http://www.1nai.med.kyushu-u.ac.jp/