The relationship between the antigen uptake site and lymphocyte activation caused to the onset of allergy in superficial lymph nodes.

• Project/Area Number: 19K07603
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Tokyo Medical University (2021-2022); Niigata University (2019-2020)
• Principal Investigator: Takeuchi Arata 東京医科大学, 医学部, 准教授 (00360579)
• Co-Investigator(Kenkyū-buntansha): 片貝 智哉 新潟大学, 医歯学系, 教授 (00324682)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: リンパ節 / 免疫監視 / ストローマ細胞

Outline of Research at the Start

リンパ節はウィルスや細菌の感染から身を守るための前衛の場である一方で、アレルギーや自己免疫疾患の発症とも関わりが深い。体に侵入した異物はリンパの流れに乗り、近隣のリンパ節に運ばれると免疫系が活性化し排除されるが、アレルギーなどを引き起こしやすい比較的分子量の大きな異物は、リンパ節の深部に位置する髄質領域に蓄積する傾向がある。本研究では髄質領域で起きる免疫応答とアレルギー発症との関係を明らかにすることを目的とする。

Outline of Final Research Achievements

It has become clear that dermal uptake antigens are related to the onset of allergy, but its induction mechanisms are remained unclear. In this study, we focused on the superficial lymph nodes (LNs) and tried to clarify the relationship between the antigen uptake site in LNs and lymphocyte activation caused to the onset of allergy. Lymph-borne highly immunogenic antigens tend to accumulate around the medullary sinus. We confirmed a part of these antigens were captured by CD11c positive cells and are internalized into deep side of LNs. In this area, specific stromal cells present and form a unique microenvironment (deep cortical periphery: DCP) where B cells are accumulated. We found B cells newly entered lymph node from blood stream migrate to follicular area via DCP. During this migration, antigen specific B cells were immediately activated in DCP area. Thus, we demonstrated the unique immune surveillance system and induction of immune response in deep side of lymph nodes.

Academic Significance and Societal Importance of the Research Achievements

リンパ節に存在するB細胞は主に皮質に存在する濾胞領域に集積する。リンパを介してリンパ節に流入する抗原は、様々な経路でこの領域に運ばれ、B細胞の活性化が誘導されることが報告されている。この様に皮質で起こるイベントについては詳細な解析が進んでいるのに対し、複雑な構造で解析が難しいリンパ節の深部には不明な点が多く残されている。今回我々はリンパ節の深部に存在し、B細胞の集積を認める微小環境に注目して、皮質とは異なる免疫作用機序が存在することを明らかにした。

Research Products

• [Journal Article] Micro- and Macro-Anatomical Frameworks of Lymph Nodes Indispensable for the Lymphatic System Filtering Function (2022)
  • Author(s): Ozawa Madoka、Nakajima Shihori、Kobayashi Daichi、Tomii Koichi、Li Nan-Jun、Watarai Tomoya、Suzuki Ryo、Watanabe Satoshi、Kanda Yasuhiro、Takeuchi Arata、Katakai Tomoya
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 10 Pages: 902601-902601
  • DOI: 10.3389/fcell.2022.902601
  • Peer Reviewed / Open Access
• [Journal Article] Tas2R signaling enhances mouse neutrophil migration via a ROCK-dependent pathway (2022)
  • Author(s): Kobayashi Daichi、Watarai Tomoya、Ozawa Madoka、Kanda Yasuhiro、Saika Fumihiro、Kiguchi Norikazu、Takeuchi Arata、Ikawa Masahito、Matsuzaki Shinsuke、Katakai Tomoya
  • Journal Title: Frontiers in Immunology Volume: 13 Pages: 973880-973880
  • DOI: 10.3389/fimmu.2022.973880
  • Peer Reviewed / Open Access
• [Journal Article] Lymph node stromal cells: diverse meshwork structures weave functionally subdivided niches (2021)
  • Author(s): Takeuchi, A., Ozawa, M., Cui, G., Ikuta, K., and Katakai, T.
  • Journal Title: Curr. Top. Microbiol. Immunol. Volume: 434 Pages: 103-121
  • DOI: 10.1007/978-3-030-86016-5_5
  • ISBN: 9783030860158, 9783030860165
  • Peer Reviewed
• [Journal Article] Transdermal entry of yeast components elicits transient B cell-associated responses in skin-draining lymph nodes (2020)
  • Author(s): Rahman Md. Azizur、Kanda Yasuhiro、Ozawa Madoka、Kawamura Toshihiko、Takeuchi Arata、Katakai Tomoya
  • Journal Title: Cellular Immunology Volume: 355 Pages: 104159-104159
  • DOI: 10.1016/j.cellimm.2020.104159
  • Peer Reviewed / Open Access
• [Presentation] リンパ節の皮髄境界面は新規の間質細胞サブセットで構成され、リンパ球に抗原認識の場を提供する (2022)
  • Author(s): 竹内新、神田泰洋、小澤まどか、町山裕亮、横須賀忠、片貝智哉
  • Organizer: Kyoto T cell Conference
• [Presentation] Deep cortex periphery reticular cells attract newly supplied B cells and provide a place to recognize antigens efficiently in early time point of exposure. (2020)
  • Author(s): Arata Takeuchi, Madoka Ozawa, Yasuhiro Kanda, Tomoya Katakai
  • Organizer: Keystone Symposia
  • Int'l Joint Research
• [Presentation] Newly supplied B cells from blood migrate to follicular area though deep cortex periphery within lymph node. (2019)
  • Author(s): Arata Takeuchi, Madoka Ozawa, Yasuhiro Kanda, Tomoya Katakai
  • Organizer: 日本免疫学会