Basic research about allergic rhinitis with CpG-DNA

• Project/Area Number: 22791581
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: University of Fukui
• Principal Investigator: KUBO Seita 福井大学, 医学部・附属病院, 助教 (80401983)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: CpG / B細胞 / PD-L1 / T細胞 / 共刺激分子 / B7RP-1 / CD30 / アレルギー性鼻炎

Research Abstract

Co-stimulatory molecules are important for regulating T cell activation and immune response. PD-L1 has emerged as an important immune modulator that can block T cell receptor signaling. We have investigated whether PD-L1 could be expressed in human B cells stimulated by CpG-DNA. CpG-DNA strongly induced the coinhibitory molecule ligand, PD-L1 of human B cells. Results show that nuclear factor-kappa B(NF-kB) signaling is involved directly in CpG-DNA-induced PD-L1 expression in human B cells. We sought to determine the effect of CpG-DNA-treated B cells on Th2 cytokine production in Cry j 1(Japanese pollen antigen)-stimulated human CD4-positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG-DNA-treated B cells reduced Cry j 1-induced IL-5 and IL-13 production in CD4-positive cells. When the binding of PD-1 to PD-L1 was inhibited by PD-1-Ig, this chimera-molecule reversed the previously described reductions in IL-5 and IL-13 production. These results indicate that CpG-DNA induces the coinhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of costimulatory molecule ligands that can promote Th2 inflammatory responses.

Research Products

• [Journal Article] CpG-DNA induces CD274-expression in human B cells and suppresses Th2 cytokine production in pollen antigen-stimulated CD4-positive cells (2012)
  • Author(s): 窪誠太
  • Journal Title: Clinical and Experimental Immunology Volume: (In press)
  • Peer Reviewed
• [Journal Article] CpG-DNA induces CD274-expression in human B cells and suppresses Th2 cytokine production in pollen antigen-stimulated CD4-positive cells
  • Author(s): Seita Kubo, Takechiyo Yamada, Yoko Osawa, Yumi Ito, Norihiko Narita and Shigeharu Fujieda
  • Journal Title: Clinical and Experimental Immunology Volume: (in press)
  • Peer Reviewed
• [Presentation] CpG-ODN induces CD274 expression on human B cells and CpG ODN-treated B cells decreased IL-5 production from antigen-stimulated human CD4+cells (2012)
  • Organizer: International Conference on Drug Discovery and Therapy
  • Place of Presentation: Dubai
  • Year and Date: 2012-02-15
• [Presentation] CpG-ODN induces CD274 expression on human B cells and CpG ODN-treated B cells decreased IL-5 production from antigen-stimulated human CD4+ cells (2012)
  • Author(s): 窪誠太
  • Organizer: International Conference on Drug Discovery and Therapy
  • Place of Presentation: ドバイ、UAE(招待講演)
  • Year and Date: 2012-02-15
• [Presentation] CpG-DNA induces CD274 expression on human B cells (2011)
  • Organizer: International Symposium on Infection and Allergy of the Nose
  • Place of Presentation: Tokyo
  • Year and Date: 2011-09-21
• [Presentation] CpG-DNA induces CD274 expression on human B cells (2011)
  • Author(s): 窪誠太
  • Organizer: International Symposium on Infection and Allergy of the Nose
  • Place of Presentation: 東京
  • Year and Date: 2011-09-21
• [Presentation] CpG-DNA induces PD-L1 (CD274) expression on human B cells (2010)
  • Author(s): 窪誠太
  • Organizer: International Symposium on Tonsils and Mucosal Barriers of the Upper Airways
  • Place of Presentation: 旭川市
  • Year and Date: 2010-07-07