Regulatory mechanism of IgA production by plasmacytoid dendritic cells and its therapeutic application for IgA nephrophathy

• Project/Area Number: 21790459
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TEZUKA Hiroyuki Tokyo Medical and Dental University, 難治疾患研究所, 助教 (30375258)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: IgA / IgA腎症 / plasmacytoid DC / Tip-DC / type I IFN / Type I IFN

Research Abstract

We here showed that plasmcytoid dendritic cells (pDCs) present in the gut-associated lymphoid tissues (GALT) induced substantially higher amounts of IgA production by B cells than conventional dendritic cells (cDCs). The pDC-mediated IgA production was dependent on APRIL and BAFF. Moreover, pDC expression of APRIL and BAFF was dependent on commensal bacteria-dependent type I IFNs production by GALT stromal cells under steady-state conditions.

Research Products

• [Journal Article] Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction. (2011)
  • Author(s): Tezuka, H., Abe, Y., Asano, J., Sato, T., Liu, J., Iwata, M., Ohteki, T.
  • Journal Title: Immunity 34 Pages: 247-257
  • Peer Reviewed
• [Journal Article] T細胞非依存性IgA生産誘導における形質細胞様樹状細胞の質的優位性 (2011)
  • Author(s): 樗木俊聡、手塚裕之
  • Journal Title: 細胞工学 30 Pages: 376-380
• [Journal Article] Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction (2011)
  • Author(s): Tezuka, H.
  • Journal Title: Immunity Volume: 34 Pages: 247-257
  • Peer Reviewed
• [Journal Article] A gas governing mucosal immunity. (2010)
  • Author(s): Tezuka, H., Ohteki, T.
  • Journal Title: Vaccine 28 Pages: 8039-8040
  • Peer Reviewed
• [Journal Article] Regulation of intestinal homeostasis by dendritic cells. (2010)
  • Author(s): Tezuka, H., Ohteki, T.
  • Journal Title: Immunological Review 234 Pages: 247-258
  • Peer Reviewed
• [Journal Article] Role of SIRPα in regulation of mucosal immunity in the intestine. (2010)
  • Author(s): Kanazawa, Y., Saito, Y., Supriatna, Y., Tezuka, H., Kotani, T., Murata, Y., Okazawa, H., Ohnishi, H., Kinouchi, Y.,Nojima, Y., Ohteki, T., Shimosegawa, T., Matozaki, T.
  • Journal Title: Genes Cells 15 Pages: 1189-1200
  • Peer Reviewed
• [Journal Article] TNF/iNOS 産生DCとIgA分泌 (2010)
  • Author(s): 樗木俊聡、手塚裕之
  • Journal Title: 医学のあゆみ 234 Pages: 453-457
• [Journal Article] A gas governing mucosal immunity (2010)
  • Author(s): Tezuka, H.
  • Journal Title: Vaccine Volume: 28 Pages: 8039-8040
  • Peer Reviewed
• [Journal Article] Regulation of intestinal homeostasis by dendritic cells (2010)
  • Author(s): Tezuka, H.
  • Journal Title: Immunological review Volume: 234 Pages: 247-258
  • Peer Reviewed
• [Journal Article] Regulation of intestinal homeostasis by dendritic cells (2010)
  • Author(s): 手塚裕之
  • Journal Title: Immunological Reviews 234 Pages: 247-258
  • Peer Reviewed
• [Journal Article] 粘膜関連リンパ組織におけるT細胞非依存性 IgAクラススイッチ誘導機構 (2009)
  • Author(s): 手塚裕之、安部由紀子、樗木俊聡
  • Journal Title: 臨床免疫.アレルギー科 52 Pages: 422-430
  • NAID: 40016880979
• [Journal Article] 消化管粘膜におけるIgA 生産機構 (2009)
  • Author(s): 手塚裕之、安部由紀子、樗木俊聡
  • Journal Title: 炎症と免疫 17 Pages: 568-574
• [Journal Article] 消化管粘膜におけるIgA生産機構 (2009)
  • Author(s): 手塚裕之
  • Journal Title: 炎症と免疫 17 Pages: 86-92
• [Journal Article] 粘膜関連リンパ組織におけるT細胞非依存性IgAクラススイッチ誘導機構 (2009)
  • Author(s): 手塚裕之
  • Journal Title: 臨床免疫・アレルギー科 52 Pages: 422-430
  • NAID: 40016880979
• [Presentation] 腸内細菌と粘膜免疫系との相互作用に関する新知見 (2010)
  • Author(s): 手塚裕之
  • Organizer: 第51回千葉造血幹細胞移植研究会
  • Place of Presentation: 千葉
  • Year and Date: 2010-04-17
• [Presentation] 腸内細菌と粘膜免疫系の相互作用に関する新知見 (2010)
  • Author(s): 手塚裕之
  • Organizer: 第51回千葉造血幹細胞移植研究会
  • Place of Presentation: バーディーホテル(千葉)
  • Year and Date: 2010-04-17
• [Presentation] Critical role for type I IFNs in pDC-induced T cell-independent IgA production. (2009)
  • Author(s): Tezuka, H., Abe, Y., Ohteki, T.
  • Organizer: 第39回日本免疫学会総会.学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Critical role for type I IFNs in pDC-induced T cell-independent IgA production (2009)
  • Author(s): Tezuka, H.
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Book] 粘膜系樹状細胞(誘導組織) (清野宏編) 臨床粘膜免疫学 (2010)
  • Author(s): 手塚裕之、安部由紀子、樗木俊聡
  • Publisher: シナジー、東京
• [Book] 粘膜系樹状細胞(誘導組織)(清野宏編)(臨床粘膜免疫学)東京 (2010)
  • Author(s): 手塚裕之
  • Publisher: シナジー
• [Remarks] ホームページ等
  • URL: http://www.tmd.ac.jp/mri/bre/index.html