The analysis of TLR10 signaling pathway for elucidating the pathogenesis of allergic diseases.

• Project/Area Number: 25860854
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Kubota Kazuo 岐阜大学, 医学部附属病院, 助教 (10526940)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 自然免疫 / Toll様受容体

Outline of Final Research Achievements

The aim of this study was to elucidate the pathophysiology of allergic diseases associated with Toll like receptor (TLR) signaling through basic research by proteomics analysis of human TLR10. We have attempted to establish an in vitro experimental system to mimic the interaction between intracellular Toll/IL-1 receptor (TIR) domains of TLR family including TLR10. The production and the analysis of the chimeric TIR proteins derived from different TLRs fused with an additional domain to N-terminus for forced dimerization was performed to investigate whether these fusion proteins possess bioactivity. First, the optimization experiment was performed using TLR1 and TLR2. In the similar condition, TLR2 combined with TLR6 could activate NF-κB signaling. On the other hand, the NF-κB activation induced by TLR2 combined with TLR10 was not observed. These results suggest that TLR10 may play as a potent negative regulator in TLR2 signaling pathway.

Research Products

• [Journal Article] The long-term health impact and potential predictors of cardiopulmonary arrest in patients with childhood-onset psychomotor impairments. (2016)
  • Author(s): Kubota K, Shimizu-Motohashi Y, Saito T, Akatsuka S, Takeshita E, Ishiyama A, Komaki H, Nakagawa E, Sugai K, Sasaki M.
  • Journal Title: Brain Dev. Volume: 38 Issue: 4 Pages: 392-398
  • DOI: 10.1016/j.braindev.2015.10.005
  • Peer Reviewed
• [Journal Article] De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance. (2015)
  • Author(s): Ohba, C., K. Haginoya, H. Osaka, K. Kubota, A. Ishiyama, T. Hiraide, H. Komaki, M. Sasaki, S. Miyatake, M. Nakashima, Y. Tsurusaki, N. Miyake, F. Tanaka, H. Saitsu, and N. Matsumoto
  • Journal Title: J Hum Genet Volume: 60 Issue: 12 Pages: 739-42
  • DOI: 10.1038/jhg.2015.108
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 注意欠如・多動性障害における脳波異常と薬物治療の検討. (2015)
  • Author(s): 久保田 一生, 仲村 貞郎, 稲垣 真澄, 中川 栄二.
  • Journal Title: 小児科臨床 Volume: 68 Pages: 2083-2088
  • Peer Reviewed
• [Journal Article] Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation. (2015)
  • Author(s): Kubota K, Saito Y, Ohba C, Saitsu H, Fukuyama T, Ishiyama A, Saito T, Komaki H, Nakagawa E, Sugai K, Sasaki M, Matsumoto N.
  • Journal Title: Brain Dev. Volume: 37 Issue: 1 Pages: 158-162
  • DOI: 10.1016/j.braindev.2014.03.001
  • Peer Reviewed
• [Journal Article] Facial palsy as an unusual presenting symptom associated with acute myeloid leukemia. (2014)
  • Author(s): Kubota K, Ozeki M, Hori T, Kanda K, Funato M, Asano T, Fukao T, Kondo N.
  • Journal Title: Pediatr Int. Volume: 56 Issue: 4 Pages: 37-40
  • DOI: 10.1111/ped.12384
  • Peer Reviewed
• [Journal Article] Clinical and genetic characterization of Japanese sporadic cases of periodic Fever, aphthous stomatitis, pharyngitis and adenitis syndrome from a single medical center in Japan. (2014)
  • Author(s): Kubota K, Ohnishi H, Teramoto T, Kawamoto N, Kasahara K, Ohara O, Kondo N.
  • Journal Title: J Clin Immunol. Volume: 34 Issue: 5 Pages: 584-593
  • DOI: 10.1007/s10875-014-0043-2
  • Peer Reviewed
• [Journal Article] Functional assessment of the mutational effects of human IRAK4 and MyD88 genes. (2014)
  • Author(s): Yamamoto T, Tsutsumi N, Tochio H, Ohnishi H, Kubota K, Kato Z, Shirakawa M, Kondo N.
  • Journal Title: Mol Immunol Volume: 58(1) Issue: 1 Pages: 66-76
  • DOI: 10.1016/j.molimm.2013.11.008
  • Peer Reviewed