Functional analysis of Sortilin in innate immune cells

• Project/Area Number: 25870851
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry; General medical chemistry
• Research Institution: Kanazawa Medical University
• Principal Investigator: YABE-WADA Toshiki 金沢医科大学, 医学部, 助教 (10451634)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 自然免疫 / サイトカイン / Toll様受容体

Outline of Final Research Achievements

Plasmacytoid dendritic cells (pDCs) are bone marrow-derived cells that sense viruses through Toll-like receptor 9 (TLR9) and TLR7, and secrete large amounts of type I interferon (IFN) in response to viruses. It is known that abnormal activation of pDCs causes several human pathologies, such as systemic lupus erythematosus. Here we report that Sortilin functions as cytokine carrier in pDCs. Knockdown of Sortilin in pDC indicated reduction of IFN-α secretion, while IFNA2 transcription activity was not influenced by knockdown. Our findings suggest that Sortilin is involved in exocytic trafficking of IFN-α in pDC.

Research Products

• [Journal Article] The iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase. (2014)
  • Author(s): Avery G Frey, Anjali Nandal, Jong Hwan Park, Pamela M Smith, Toshiki Yabe, Moon-Suhn Ryu, Manik C Ghosh, Jaekwon Lee, Tracey A Rouault, Myung Hee Park, Caroline Philpott
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 111 Issue: 22 Pages: 8031-8036
  • DOI: 10.1073/pnas.1402732111
  • Peer Reviewed
• [Journal Article] Each member of the PCBP family exhibits iron chaperone activity toward ferritin (2013)
  • Author(s): Sebastien Leidgens, Kimberley Z. Bullough, Haifeng Shi, Fengmin Li, Minoo Shakoury-Elizeh, Toshiki Yabe, Poorna Subramanian, Emory Hsu, Navin Natarajan, Anjali Nandal, Timothy L. Stemmler, Caroline C. Philpott
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 24 Pages: 17791-17802
  • DOI: 10.1074/jbc.m113.460253
  • Peer Reviewed
• [Presentation] A regulatory role of secretory leukoprotease inhibitor (SLPI) in allergic effector cells. (2013)
  • Author(s): Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Toshiyuki Takai, Akira Nakamura
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉・幕張メッセ
• [Presentation] 好塩基球・好酸球におけるSLPIの制御機構の解明 (2013)
  • Author(s): 松葉慎太郎，和田俊樹，武田和也，佐藤哲也，須山幹太，高井俊行，中村 晃
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京・ホテルニューオータニ