Elucidation of the mechanism for itch induction by using a novel mouse model of atopic skin inflammation

• Project/Area Number: 26670287
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pain science
• Research Institution: Kyushu University
• Principal Investigator: Fukui Yoshinori 九州大学, 生体防御医学研究所, 教授 (60243961)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: シグナル伝達 / 生体分子 / 細胞・組織

Outline of Final Research Achievements

We have developed a novel mouse model that spontaneously causes atopic skin inflammation with severe scratching behavior. The majority of infiltrating cells were CD4+ T cells, and they produced a large amount of IL-31 upon stimulation. By crossing these mice with mice lacking oncostatin M receptor, we have shown that IL-31 signaling plays a key role in the disease development. In addition, we have identified a molecule critical for IL-31 production by CD4+ T cells.

Research Products

• [Journal Article] Parallel regulation of VHL disease by pVHL-mediated degradation of B-Myb and HIF-α. (2016)
  • Author(s): Okumura F, Uematsu K, Byrne S, Hirano M, Joo-Okumura A, Nishikimi A, Shuin T, Fukui Y, Nakatsukasa K, Kamura K.
  • Journal Title: Mol. Cell. Biol. Volume: in press
  • Peer Reviewed
• [Journal Article] Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus. (2015)
  • Author(s): Yanagihara T, Sanematsu F, Sato T, Uruno T, Duan X, Tomino T, Harada Y, Watanabe M, Wang Y, Tanaka Y, Nakanishi Y, Suyama M, Yoshinori F.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 8820-8820
  • DOI: 10.1038/ncomms9820
  • Peer Reviewed / Open Access
• [Journal Article] Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling. (2015)
  • Author(s): Guo X, Shi N, Cui X-B, Wang J-N, Fukui Y, Chen S-Y.
  • Journal Title: Cir. Res. Volume: 116 Issue: 10
  • DOI: 10.1161/circresaha.116.305863
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Axl phosphorylates Elmo scraffold proteins to promote Rac activation and cell invasion. (2015)
  • Author(s): Abu-Thuraia A, Gauthier R, Chidiac R, Fukui Y, Screaton RA, Gratton JP, Cote JF.
  • Journal Title: Mol Cell Biol. Volume: 35 Issue: 1 Pages: 76-87
  • DOI: 10.1128/mcb.00764-14
  • Peer Reviewed
• [Journal Article] DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation. (2014)
  • Author(s): Ogawa K, Tanaka Y, Uruno T, Duan X, Harada Y, et al.
  • Journal Title: J. Exp. Med. Volume: (In press) Issue: 7 Pages: 1407-1419
  • DOI: 10.1084/jem.20131926
  • Peer Reviewed / Open Access
• [Journal Article] DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation. (2014)
  • Author(s): Watanabe M, Terasawa M, Miyano K, Yanagihara T, Uruno T, Sanematsu F, Nishikimi A, Cote JF, Sumimoto H, Fukui Y.
  • Journal Title: J Immunol. Volume: 193 Issue: 11 Pages: 5660-5667
  • DOI: 10.4049/jimmunol.1400885
  • Peer Reviewed / Open Access
• [Presentation] マスト細胞の脱顆粒反応におけるDOCK5の役割とその制御機構 (2015)
  • Author(s): 福井宣規
  • Organizer: 第64回日本アレルギー学会学術大会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2015-05-27
  • Invited
• [Presentation] Critical roles of DOCK family proteins in migration and activation of leukocytes. (2015)
  • Author(s): Fukui Y
  • Organizer: Keystone Symposium
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-01-13 – 2015-01-18
  • Invited
• [Presentation] The role of DOCK8 in migration and activation of effector CD4+ T cells during immune responses. (2014)
  • Author(s): Harada Y et sl
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Patent(Industrial Property Rights)] アトピー性皮膚炎モデル非ヒト動物及びその使用 (2016)
  • Inventor(s): 福井宣規、山村和彦、宇留野武人、古江増隆、
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-034510
  • Filing Date: 2016-02-25