Factors in the pathogenesis and exacerbation of eosinophilic sinusiti

• Project/Area Number: 17K11367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Toho University
• Principal Investigator: WADA Kota 東邦大学, 医学部, 教授 (20307482)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 好酸球性副鼻腔炎 / 上皮細胞 / 線維芽細胞 / TSLP / Th2サイトカイン / ペリオスチン / 難治性 / IL-33 / 喘息 / ウィルス感染 / ウィルス / 難治性副鼻腔炎 / 慢性副鼻腔炎 / 気道上皮細胞 / IL-３３

Outline of Final Research Achievements

The study was performed using sinus-derived epithelial cells and fibroblasts obtained from nasal polyps, and stimulation was performed using Poly I;C, a ligand for TLR3. TSLP was not detected when epithelial cells were stimulated with Th2 cytokines. However, when Poly I;C stimulation was performed on epithelial cells, TSLP could be detected, and the addition of Th2 cytokines and Poly I;C increased TSLP production more than the addition of Poly I;C alone, especially in severe cases of ECRS. Local lymphocytes were also studied. In sinusitis with polyps, the CD4+ T cell/B cell ratio was predominantly higher in ECRS compared to non-ECRS.

Academic Significance and Societal Importance of the Research Achievements

難治である好酸球性副鼻腔炎は今までは手術とステロイドのみが効果的な治療であった。昨今は分子標的薬（抗IL-4,IL-13背レプター抗体療法）が保険適応となった。今回の治療で、TSLPもターゲットサイトカインとなりうることが示された。しかし、ＴＳＬＰのみをブロックするのではなく、Ｔｈ２サイトカインも同時にブロックするカクテル療法のような治療の開発が重要である可能性が示唆された。また、ペリオスチンも同様にターゲットとなりうると予想される。今後、これらの基礎研究が臨床の現場へ貢献できると信じている。

Research Products

• [Journal Article] Anatomical Factors that Can Predict the Structure of Lamina Papyracea for Endoscopic Sinus Surgery (2021)
  • Author(s): Shinya Ohira, Kentaro Matsuura, Hidehito Matsui, Mitsuto Nakamura, Kazuhisa Kamiyama, Riko Kajiwara, Akiko Inoue, Kota Wada
  • Journal Title: The Laryngoscope Volume: 131 (1) Issue: 1
  • DOI: 10.1002/lary.28644
  • Peer Reviewed / Open Access
• [Journal Article] High CD4+ T-Cell/B-Cell Ratio in the Paranasal Sinus Mucosa of Patients with Eosinophilic Chronic Rhinosinusitis (2020)
  • Author(s): Akiko Inoue, Yuriko Tanaka, Shinya Ohira, Kentaro Matsuura, Motonari Kondo, Kota Wada
  • Journal Title: International Archives of Otorhinolaryngology Volume: 10 Issue: 03 Pages: 1-1
  • DOI: 10.1055/s-0040-1715587
  • Peer Reviewed / Open Access
• [Journal Article] Mouthwash-Based Highly Sensitive Pyro-Genotyping for Nine Sexually Transmitted Human Papilloma Virus Genotypes (2020)
  • Author(s): Yoshiyuki Watanabe ＊, Seto Yukiko, Ritsuko Oikawa, Takara Nakazawa, Hanae Furuya, Hidehito Matsui, Sachiko Hosono, Mika Noike, Akiko Inoue, Hiroyuki Yamamoto, Fumio Itoh, Kota Wada
  • Journal Title: International Journal of Molecular Sciences Volume: 21 (10) Issue: 10 Pages: 3697-3697
  • DOI: 10.3390/ijms21103697
  • Peer Reviewed / Open Access
• [Presentation] 酸球性副鼻腔炎における難治化因子の解明により下気道疾患の病因を探る (2021)
  • Author(s): 和田弘太、井上彰子、田中ゆり子
  • Organizer: 第157回東邦医学会例会
• [Presentation] More severe ECRS patients produce more TSLP in the paranasal sinus mucosa (2020)
  • Author(s): Akiko Inoue, Yuriko Tanaka, Motonari Kondo, Hidehito Matsui, Takara Nakazawa, Shinya Ohira, Hiroshi Osafune, Kota Wada
  • Organizer: JSA/WAO Joint Congress 2020