Functional analysis of the protein phosphatase expressed in dendritic cells

• Project/Area Number: 25461468
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Gunma University
• Principal Investigator: KANEKO YORIAKI 群馬大学, 医学部附属病院, 講師 (00334095)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 自己免疫疾患 / ホスファターゼ / 自己免疫 / 樹状細胞 / Shp-1 / SHP-1

Outline of Final Research Achievements

We generated a conditional knockout mouse (Shp-1 cKO) in which Shp-1, an intracytoplasmic tyrosine phosphatase, is specifically depleted in dendritic cells (DCs). Shp-1 cKO developed autoimmune nephritis with aging, which was characterized by massive infiltration of macrophages and T cells. The cells prepared from the kidneys of Shp-1 cKO were able to produce large amounts of inflammatory cytokines, therefore we conclude Shp-1 in DCs acts as a negative regulator for the development of autoimmune nephritis.

Research Products

• [Journal Article] Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs (2015)
  • Author(s): Washio K, Kotani T, Saito Y, Respatika D, Murata Y, Kaneko Y, Okazawa H, Ohnishi H, Fukunaga A, Nishigori C, Matozaki T.
  • Journal Title: Genes Cells Volume: - Issue: 6 Pages: 00-00
  • DOI: 10.1111/gtc.12238
  • Peer Reviewed / Open Access
• [Journal Article] SIRPα signaling regulates podocyte structure and function (2013)
  • Author(s): Takahashi S, Tomioka M, Hiromura K, Sakairi T, Hamatani H, Watanabe M, Ikeuchi H, Kaneko Y, Maeshima A, Aoki T, Ohnishi H, Matozaki T, Nojima Y
  • Journal Title: Am J Physiol Renal Physiol Volume: 305 Issue: 6 Pages: 861-70
  • DOI: 10.1152/ajprenal.00597.2012
  • Peer Reviewed
• [Presentation] Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp-1 induces autoimmune nephritis characterized by infiltration of dendritic cell and Th1 cell (2015)
  • Author(s): WATANABE Mitsuharu, KANEKO Yoriaki, HIROMURA Keiju, OHISHI Yuko, KINOSHITA Masato, SAITO Yasuyuki, OHNISHI Hiroshi, MATOZAKI Takashi, NOJIMA Yoshihisa
  • Organizer: The 44th annual meeting of the Japanese Society of Immunology
  • Place of Presentation: Sapporo
  • Year and Date: 2015-11-18
• [Presentation] Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp1 induces enhanced production of inflammatory cytokines by toll-like receptor-mediated stimulation (2015)
  • Author(s): OHISHI Yuko, KANEKO Yoriaki, WATANABE Mitsuharu, KINOSHITA Masato, HIROMURA Keiju, SAITO Yasuyuki, OHNISHI Hiroshi, MATOZAKI Takashi, NOJIMA Yoshihisa
  • Organizer: The 44th annual meeting of the Japanese Society of Immunology
  • Place of Presentation: Sapporo
  • Year and Date: 2015-11-18
• [Presentation] Dendritic Cell-Specific Shp-1-Knockout Mice Spontaneously Develop Unique Glomerulo- and Tubulointerstitial Nephritis (2015)
  • Author(s): Mitsuharu Watanabe, Keiju Hiromura, Yoriaki Kaneko, Masato Kinoshita, Yuko Ohishi, Toru Sakairi, Hidekazu Ikeuchi, Akito Maeshima, Hiroshi Ohnishi, Takashi Matozaki, Yoshihisa Nojima
  • Organizer: Kidney Week 2015, American Society of Nephrology
  • Place of Presentation: San Diego, CA
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Essential role of SIRPα on dendritic cells in organizing and homeostasis of the spleen (2014)
  • Author(s): Washio Ken, Kotani Takenori, Respatika Datu, Murata Yoji, Saito Yasuyuki, Kaneko Yoriaki, Okazawa Hideki, Ohnishi Hiroshi, Fukunaga Atsushi, Nishigori Chikako, Matozaki Takashi
  • Organizer: The 43rd annual meeting of the Japanese society of immunology
  • Place of Presentation: Kyoto
  • Year and Date: 2014-12-04
• [Presentation] Immunological analysis of autoimmune nephritis observed in DC-specific Shp1 conditional knockout mice. (2014)
  • Author(s): Watanabe Mitsuharu, Kaneko Yoriaki, Hiromura Keiju, Ohishi Yuko, Kinoshita Masato, Ohnishi Hiroshi, Matozaki Takashi, Nojima Yoshihisa
  • Organizer: The 43rd annual meeting of the Japanese society of immunology
  • Place of Presentation: Kyoto
  • Year and Date: 2014-12-04