Molecular mechanisms of regulatory B cell inhibition on skin immunological diseases

• Project/Area Number: 23390281
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Tsukuba (2013); Kanazawa University (2011-2012)
• Principal Investigator: FUJIMOTO Manabu 筑波大学, 医学医療系, 教授 (90272591)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 免疫 / B細胞 / 皮膚免疫 / アレルギー / 自己免疫疾患 / 細胞 / 皮膚疾患

Research Abstract

Signal transduction mechanisms responsible for IL-10 production in regulatory B cells were analyzed. BLNK is an important adaptor protein in B cell signal transduction. B cells from BLNK-deficient mice showed diminished IL-10 production in CD1dhiCD5+ B cells. Accordingly, BLNK-deficient mice exhibited augmented contact hypersensitivity response. CD1dhiCD5+ B cells from BLNK-deficient mice showed impaired Stat3 activation, which was dependent on Btk activity. Moreover, exogenous addition of IL-10 in culture markedly increased the number of IL-10-producing B cells, suggesting the presence of positive feedback loop provided by IL-10 stimulation.

Research Products

• [Journal Article] Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement. (2014)
  • Author(s): Kaji K, Fertig N, Medsger TA Jr, Satoh T, Hoshino K, Hamaguchi Y, Hasegawa M, Lucas M, Schnure A, Ogawa F, Sato S, Takehara K, Fujimoto M, Kuwana M.
  • Journal Title: Arthritis Care Res Volume: 66 Issue: 4 Pages: 575-84
  • DOI: 10.1002/acr.22163
  • Peer Reviewed
• [Journal Article] BLNK expression contributes to controlling allergic and autoimmune diseases by mediating IL-10 production in regulatory B cells (2013)
  • Author(s): Jin G, Hamaguchi Y, Matsushita T, Hasegawa M, Huu DL, Ishiura N, Naka K, Hirao A, Takehara K, Fujimoto M
  • Journal Title: J Allergy Clin Immunol Volume: 131 Issue: 6 Pages: 1674-1682
  • DOI: 10.1016/j.jaci.2013.01.044
  • Peer Reviewed
• [Journal Article] Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease (2013)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, T akehara K, T edder TF, Fujimoto M
  • Journal Title: Blood Volume: 121 Issue: 16 Pages: 3274-83
  • DOI: 10.1182/blood-2012-11-465658
  • 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
• [Journal Article] Basophils and mast cells play critical roles for leukocyte recruitment in IgE-mediated cutaneo us reverse passive Arthus reaction. (2012)
  • Author(s): Jin G, Matsushita T, Hamaguchi Y, Le H uu D, Ishii T, Hasegawa M, Obata K Kar asuyama H, Takehara K, Fujimoto M
  • Journal Title: J Dermatol Sci. Volume: 67 (3) Issue: 3 Pages: 181-189
  • DOI: 10.1016/j.jdermsci.2012.06.005
  • Peer Reviewed
• [Journal Article] Potential roles of interleukin 17A in the development of skin fibrosis (2012)
  • Author(s): Okamoto Y, Hasegawa M, Matsushita T, Hamaguchi Y, Huu DL, Iwakura Y, Fujimoto M, T akehara K
  • Journal Title: Arthritis Rheum Volume: 64 Issue: 11 Pages: 3726-35
  • DOI: 10.1002/art.34643
  • Peer Reviewed
• [Journal Article] IL-6 blockade attenuates the development of murine sclerodermatous chronic graft-versus-host disease (2012)
  • Author(s): Le Huu D, Matsushita T, Jin G, Hamaguchi Y, Hasegawa M, T akehara K, Fujimoto M
  • Journal Title: J Invest Dermatol Volume: 132 Issue: 12 Pages: 2752-61
  • DOI: 10.1038/jid.2012.226
  • Peer Reviewed
• [Presentation] Regulatory B cells in skin disease (2013)
  • Author(s): Fujimoto M
  • Organizer: International Meeting of Investigative Dermatology
  • Place of Presentation: Edinburgh, UK
  • Year and Date: 2013-05-10