Trial in the regulation of mast cell function by targeting autophagy related protein

• Project/Area Number: 24591470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Juntendo University
• Principal Investigator: USHIO HIROKO 順天堂大学, 医学(系)研究科(研究院), 准教授 (30317391)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マスト細胞 / オートファジー / 顆粒形成

Outline of Final Research Achievements

Autophagy is the essential function for controlling various biological responses including starvation, homeostatic turnover of long-lived proteins, and invasion of bacteria. However, a role for autophagy in the development and function of mast cells is largely unknown. We recently have reported that autophagy-related gene (Atg) 7, a critical enzyme for autophagosome formation, has relevance of mast cell functions using bone marrow-derived mast cells (BMMCs) from Atg7-deficient mice. To define further the roles for autophagy in mast cell function, we analyzed the changes of Atgs in mast cells after IgE-mediated activation using PCR-array. We found further that Atg9b, Gamma-aminobutyric acid A receptor-associated protein-like 1 (GABARAPL1), a homolog of Atg8, were also associated in the degranulation and regranulation of mast cells. Collectively, these results may lead to help modifing the mast cell function by targeting these proteins.

Research Products

• [Journal Article] Roles of retinoic acid-inducible gene-I-like receptors (RLRs), Toll-like receptor (TLR) 3 and 2'-5' oligoadenylate synthetase as viral recognition receptors on human mast cells in response to viral infection. (2015)
  • Author(s): Tsutsui-Takeuchi M, Ushio H, Fukuda M, Yamada T, Niyonsaba F, Okumura K, Ogawa H, Ikeda S.
  • Journal Title: Immunol Res Volume: 61 Issue: 3 Pages: 240-9
  • DOI: 10.1007/s12026-014-8617-x
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Host Defense (Antimicrobial) Peptide, Human β-Defensin-3, Improves the Function of the Epithelial Tight-Junction Barrier in Human Keratinocytes. (2014)
  • Author(s): Kiatsurayanon C, Niyonsaba F, Smithrithee R, Akiyama T, Ushio H, Hara M, Okumura K, Ikeda S, Ogawa H.
  • Journal Title: J invest Deramatol Volume: 143 Issue: 8 Pages: 2163-73
  • DOI: 10.1038/jid.2014.143
  • Peer Reviewed
• [Journal Article] Expression and Functional Characterization of Retinoic Acid-Inducible Gene-I-Like Receptors of Mast Cells in Response to Viral Infection. (2012)
  • Author(s): Fukuda M, Ushio H, Kawasaki J, Niyonsaba F, Takeuchi M, Baba T, Hiramatsu K, Okumura K, Ogawa H.
  • Journal Title: Journal of Innate Immunity Volume: 5 Issue: 2 Pages: 163-173
  • DOI: 10.1159/000343895
  • Peer Reviewed
• [Journal Article] Interleukin-36 cytokines enhance the production of host defense peptides psoriasin and LL-37 by human keratinocytes through activation of MAPKs and NF-κB (2012)
  • Author(s): Nguyen TT
  • Journal Title: J Dermatol Sci Volume: 68 Issue: 1 Pages: 63-6
  • DOI: 10.1016/j.jdermsci.2012.07.010
  • Peer Reviewed
• [Presentation] Roles of autophagy in degranulation and regranulation of mast cells (2014)
  • Author(s): YAMADA T, USHIO H, NIYONSABA F, OKUMURA K,IKEDA S, OGAWA H.
  • Organizer: 第113回日本皮膚科学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-05-30 – 2014-06-01
• [Presentation] ヒトマスト細胞におけるRIG-I様受容体(RLRs)を介した抗ウイルス免疫応答 (2014)
  • Author(s): 竹内瑞穂、牛尾博子、福田稔、河崎純子、François Niyonsaba、小川秀興、奥村康、池田志斈
  • Organizer: 第113回日本皮膚科学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-05-30 – 2014-06-01
• [Presentation] IL-36 cytokines enhance the production of host defense peptides LL-37 and psoriasin by human keratinocytes through activation of MAPKs and NF-kB (2013)
  • Author(s): Akiyama T, Nguyen TT, Niyonsaba F, Smithrithee R, Kiatsurayanon C, Ushio H, Okumura K, Ogawa H, Ikeda S
  • Organizer: 2013 International Investigative Dermatology
  • Place of Presentation: Edinburgh, Scotland
• [Presentation] Characterization of virus recognition receptors: RIG-1-like receptors (RLRs) of mast cells (2013)
  • Author(s): Takeuchi M, Fukuda M, Ushio H, Kawasaki J, Niyonsaba F, Okumura K, Ikeda S, Ogawa H
  • Organizer: 2013 International Investigative Dermatology
  • Place of Presentation: Edinburgh, Scotland
• [Presentation] Effects of human β-defensins on interleukin-37 production by human keratinocytes (2013)
  • Author(s): Smithrithee R, Niyonsaba F, Kiatsurayanon C, Nguyen TT, Akiyama T, Ushio H, Ikeda S, Okumura K, Ogawa H
  • Organizer: 2013 International Investigative Dermatology
  • Place of Presentation: Edinburgh, Scotland
• [Presentation] Human β-defensin-3 improves the epithelial tight junction (TJ) barrier through activation of glycogen synthase kinase-3 (GSK-3) and protein kinase C (PKC) (2013)
  • Author(s): Kiatsurayanon C, Niyonsaba F, Smithrithee R, Nguyen TT, Akiyama T, Ushio H, Ikeda S, Okumura K, Ogawa H
  • Organizer: 2013 International Investigative Dermatology
  • Place of Presentation: Edinburgh, Scotland
• [Presentation] Analyses of nasal exhaled breath condensate in patients with allergic rhinitis (2013)
  • Author(s): Hassan S, Miwa M, Hanao M, Shiozawa A, Hirtotsu M, Ono N, Sasaki D, Hara M, Ushio H, Hirose T, Miwa M, Ikeda K, Okumura K.
  • Organizer: 16th Asian Research Symposium in Rhinology
  • Place of Presentation: Tokyo
• [Presentation] マスト細胞の細胞内dsRNA受容体の発現とウイルス応答における役割 (2012)
  • Author(s): 福田稔，牛尾博子、河﨑純子，Niyonsaba Francois、奥村康、小川秀興
  • Organizer: 第62回日本アレルギー学会
  • Place of Presentation: 大阪国際会議場
• [Presentation] Effects of IL-36 cytokines on S100A7/psoriasin and cathelicidin LL-37 expression and production by primary human keratinocytes (2012)
  • Author(s): Nguen T, ,Niyonsaba F,Akiyama T, Smithrithee R, Kiatsurayanon C, Ushio H, Ikeda S, Okumura K, Ogawa H.
  • Organizer: 第37回日本研究皮膚科学会
  • Place of Presentation: ロワジールホテル＆スパタワー那覇
• [Presentation] The expression and functional characterization of RIG-I-like receptors (RLRs) of mast cells in response to viral infection (2012)
  • Author(s): Takeuchi M, Fukuda M, Ushio H, Kawasaki J, Niyonsaba F, Okumura K, Ikeda S, Ogawa H.
  • Organizer: 第37回日本研究皮膚科学会
  • Place of Presentation: ロワジールホテル＆スパタワー那覇