The role of regulatory B cell in the pathogenesis of systemic sclerosis

• Project/Area Number: 25461686
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kanazawa University
• Principal Investigator: Matsushita Takashi 金沢大学, 大学病院, 講師 (60432126)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 全身性強皮症 / サイトカイン / 制御性B細胞 / 強皮症

Outline of Final Research Achievements

Sclerodermatous cGVHD (Scl-cGVHD) is characterized by fibrosis and autoimmune features resembling those of systemic sclerosis (SSc). Transplantation of B10.D2 bone marrow and splenocytes into irradiated-BALB/c mice is an established model of human Scl-cGVHD. To examine the role of regulatory B cells (Breg cell) in Scl-cGVHD, CD19-deficient (CD19-/-; lack of Breg cell) mice were used as donors or recipients in this model. CD19-/- donors induced more severe Scl-cGVHD than wild-type donors. Adoptive transfer of Breg cells attenuated the augmented manifestations of CD19-/- donor-induced Scl-cGVHD. The frequency of blood Breg cells was significantly lower in patients with SSc, and Breg cell levels inversely correlated with disease activity of SSc. These results suggest that decreased Breg cells contribute to the development of SSc.

Research Products

• [Journal Article] Decreased Levels of Regulatory B cells in Patients with Systemic Sclerosis: Association with autoantibody production and disease activity. (2016)
  • Author(s): Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M.
  • Journal Title: Rheumatology (Oxford). Volume: 55 Issue: 2 Pages: 263-267
  • DOI: 10.1093/rheumatology/kev331
  • NAID: 120005764209
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clinical and immunological predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III antibodies. (2015)
  • Author(s): Hamaguchi Y, Kodera M, Matsushita T, Usuda T, Kuwana M, Takehara K, and Fujimoto M
  • Journal Title: Arthritis Rheumatol Volume: 67 Issue: 4 Pages: 1045-1052
  • DOI: 10.1002/art.38994
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] B cells promote tumor immunity against B16F10 melanoma. (2014)
  • Author(s): Kobayashi T, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K, Matsushita T.
  • Journal Title: Am J Pathol. Volume: 184 Issue: 11 Pages: 3120-3129
  • DOI: 10.1016/j.ajpath.2014.07.003
  • Peer Reviewed
• [Journal Article] Regulatory B cells in mouse models of systemic lupus erythematosus (SLE). (2014)
  • Author(s): Matsushita T.
  • Journal Title: Methods Mol Biol. Volume: 1190 Pages: 195-205
  • DOI: 10.1007/978-1-4939-1161-5_14
  • ISBN: 9781493911608, 9781493911615
• [Journal Article] A crucial role of L-selectin in C protein-induced experimental polymyositis of mice. (2014)
  • Author(s): Oishi K, Hamaguchi Y, Matsushita T, Hasegawa M, Okiyama N, Dernedde J, Weinhart M, Haag R, Tedder TF, Takehara K, Kohsaka H, Fujimoto M.
  • Journal Title: Arthritis Rheumatol. Volume: mar 18 Issue: 7 Pages: 1864-71
  • DOI: 10.1002/art.38630
  • Peer Reviewed
• [Journal Article] FTY720 ameliorates murine Scl-cGVHD by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into skin (2013)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M
  • Journal Title: Arthritis Rheum Volume: in press Issue: 6 Pages: 1624-35
  • DOI: 10.1002/art.37933
  • Peer Reviewed
• [Presentation] Blockade of Syk Ameliorates the Development of Sclerodermatous Chronic Graft-Versus-Host Disease. (2014)
  • Author(s): Matsushita T, Le Huu D, Kimura H, Date M, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K
  • Organizer: ESDR 2014
  • Place of Presentation: Copenhagen
  • Year and Date: 2014-09-11 – 2014-09-23
• [Presentation] FTY720 ameliorates murine Scl-cGVHD by promoting expansion of splenic regulatory cells and inhibiting immune cell infiltration into the skin. (2013)
  • Author(s): Matsushita T, Le Huu D, Takehara K, Fujimoto M
  • Organizer: The American Association of Immunologists
  • Place of Presentation: Honolulu, USA