The role of M cells in allergic airway inflammation

• Project/Area Number: 19K21170
• Project/Area Number (Other): 18H06033 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Keio University
• Principal Investigator: Nakamura Yutaka 慶應義塾大学, 薬学部(芝共立), 特任助教 (60824456)
• Project Period (FY): 2018-08-24 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: M細胞 / 気道炎症 / 気管支炎 / 粘膜免疫 / 気管支 / アレルギー

Outline of Research at the Start

アレルギー疾患が皮膚や粘膜における異常な免疫応答であることが広く知られる一方、こうした異常な免疫応答がどのように誘導されるかは明らかでない。粘膜関連リンパ組織は、上皮層のMicrofold(M)細胞を介して粘膜管腔中の外来抗原を取り込むことで、粘膜面に免疫応答を誘導する独自の免疫誘導組織である。しかしながら、M細胞とアレルギー炎症応答との関係を明らかにした研究はなく、その解明は喫緊の課題である。本研究では、M細胞欠損マウスのアレルギー性気管支炎モデルにおける病態形成と免疫応答を評価することにより、M細胞による抗原取り込みがアレルギー性気管支炎に関与するのかについて明らかにする。

Outline of Final Research Achievements

Our results from M cell-null Spi-B or Sox8-deficient mice indicate that the development of airway mucosa-associated lymphoid tissues, like NALT and iBALT, is independent of M cells. On the other hand, the defect of Spi-B slightly reduced germinal center B cells, indicating the reduced induction of immune responses.
The Spi-B depletion exacerbated the house dust mite (HDM)-induced asthma, as represented by the increased number of macrophages infiltrating the bronchoalveolar lumen. This result suggests that M cells play an important role in the defense against airway damage.

Academic Significance and Societal Importance of the Research Achievements

これまで気道M細胞による抗原取り込みと気道炎症との関連は明確ではなかった。しかし、本研究により、気道炎症に対する宿主防御応答にM細胞による抗原取り込みが寄与していることが推測された。さらなる研究により、宿主防御応答の詳細を明らかにすることで、アレルギー病態形成におけるM細胞の役割、免疫誘導機構について解明することが可能である。

Research Products

• [Journal Article] Microfold cell-dependent antigen transport alleviates infectious colitis by inducing antigen-specific cellular immunity (2020)
  • Author(s): Nakamura Yutaka、Mimuro Hitomi、Kunisawa Jun、Furusawa Yukihiro、Takahashi Daisuke、Fujimura Yumiko、Kaisho Tsuneyasu、Kiyono Hiroshi、Hase Koji
  • Journal Title: Mucosal Immunology Volume: in press Issue: 4 Pages: 679-690
  • DOI: 10.1038/s41385-020-0263-0
  • Peer Reviewed / Open Access
• [Journal Article] Osteoprotegerin-dependent Mcell self-regulation balances gut infection and immunity. (2020)
  • Author(s): Kimura S, Nakamura Y, Kobayashi N, Shiroguchi K, KawakamiE, Mutoh M, Takahashi-Iwanaga H, Yamada T, Hisamoto M, Nakamura M, Udagawa N, Sato S, KaishoT, Iwanaga T, Hase K.
  • Journal Title: Nat Commun Volume: 11 Issue: 1 Pages: 234-234
  • DOI: 10.1038/s41467-019-13883-y
  • Peer Reviewed / Open Access
• [Journal Article] M cell-dependent antigen uptake on follicle-associated epithelium for mucosal immune surveillance (2018)
  • Author(s): Yutaka Nakamura, Shunsuke Kimura, Koji Hase
  • Journal Title: Inflammation and Regeneration Volume: 38 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s41232-018-0072-y
  • Peer Reviewed / Open Access
• [Presentation] Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity. (2020)
  • Author(s): Yutaka Nakamura
  • Organizer: The 8th Global Network Forum on Infection and Immunity
  • Int'l Joint Research
• [Presentation] Osteoprotegerin-dependent M cell self-regulation balances the gut immunity and infection (2019)
  • Author(s): Yutaka Nakamura, Shunsuke Kimura, Nobuhide Kobayashi, Katsuyuki Shiroguchi, Eiryo Kawakami, Mami Mutoh, Hiromi Takahashi-Iwanaga, Takahiro Yamada, Meri Hisamoto, Midori Nakamura, Nobuyuki Udagawa, Shintaro Sato, Tsuneyasu Kaisho, Toshihiko Iwanaga, Koji Hase
  • Organizer: 17th International Congress of Immunology
  • Int'l Joint Research
• [Presentation] M-cell-dependent antigen uptake mitigates infectious colitis by shaping mucosal barrier function (2018)
  • Author(s): Yutaka Nakamura
  • Organizer: 第47回日本免疫学会
• [Remarks] 慶應義塾大学薬学部生化学講座
  • URL: http://square.umin.ac.jp/keio-dbc/