Mechanism of mucosal immune system in human pediatric pharyngeal tonsils

• Project/Area Number: 18K09381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Ogasawara Noriko 札幌医科大学, 医学部, 講師 (00438061)
• Co-Investigator(Kenkyū-buntansha): 山本 聡 札幌医科大学, 医学部, 助教 (10588479) ; 佐藤 豊孝 札幌医科大学, 医学部, 講師 (30756474)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: RSウイルス / 小児咽頭扁桃 / M細胞 / 上皮細胞 / 咽頭扁桃上皮細胞 / 咽頭扁桃 / 小児 / 樹状細胞 / microfold cell / 鼻咽腔粘膜関連リンパ組織

Outline of Final Research Achievements

We succeeded in isolating 14 primary cultured human pediatric nasopharyngeal tonsil epithelial cells (HNTE).
HNTEs were infected GFP recombinant respiratory syncytial virus (RSV). The GFP-negative and positive cells were collected and will be analyzed by RNA sequence. We are planning to analyze what factors are expressed in HNTEs susceptible to RSV. In addition, A549, BEAS-2B and HNTEs were cultured under submerge and air-liquid interface (ALI) conditions. Following RSV infection, we treated Streptococcus pneumoniae on upper chamber. After 96 hours RSV infection, we measured barrier function and the number of viable S. pneumoniae in epithelial cell. As a result, we found that in the ALI state, unlike the submerge state, RSV infection reduces the epithelial barrier function, and S. pneumoniae infection after RSV infection further reduces the barrier function. From the above results, it suggests that the functions of epithelial cells differed under submerge and ALI conditions.

Academic Significance and Societal Importance of the Research Achievements

呼吸器に感染する微生物は人類の生活環に密接に関わり、小さなきっかけで大流行に至る潜在的脅威を持った病原体である。しかしながら多くの呼吸器感染性病原体は、予防・治療法が未確立である。本研究で示した呼吸器感染性病原体に対する対する生体の初期応答から防御に至る過程および組織・宿主特異的免疫反応の一部は将来的に、宿主独自の反応を示す作用点として、治療の標的となる可能性があり、新たな治療戦略確立に寄与する重要な意義がある。特に上皮細胞の状態が免疫応答に関わるとする成果は、咽頭扁桃焼灼・切除による免疫機能のリセットの可能性を示唆する重要な成果である。

Research Products

• [Presentation] 鼻茸を伴う慢性副鼻腔炎における2型自然リンパ球制御機構の解明 (2020)
  • Author(s): 小笠原 徳子
  • Organizer: 第59回日本鼻科学会
  • Invited
• [Presentation] Role of receptor activator of NFκB ligand and group 2 Innate lymphoid cells in type 2 inflammation in chronic rhinosinusitis with nasal polyps (2018)
  • Author(s): Noriko Ogasawara, Julie A. Poposki, Aiko I. Klingler, Bruce K. Tan, Kathryn E. Hulse, PhD1; Whitney W. Stevens, MD, PhD1; Anju T. Peters, MD1; Robert P. Schleimer, Pejman Soroosh, Ken-ichi Takano, Tetsuo Himi, Robert C. Kern, Atsushi Kato
  • Organizer: 第3回自然リンパ球国際会議
  • Int'l Joint Research