Elucidation of mechanisms for basophil maturation by using RNA-seq

• Project/Area Number: 20K16277
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Miyake Kensuke 東京医科歯科大学, 統合研究機構, 特任助教 (90814533)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 好塩基球 / 1細胞RNAシーケンス / 未熟好塩基球 / 成熟好塩基球 / 前駆細胞 / 寄生虫感染 / RNAシーケンス / 分化 / 転写因子 / アレルギー

Outline of Research at the Start

好塩基球は非常に稀少な白血球の一つであるが、最近の研究により好塩基球がアレルギー反応においてきわめて重要な役割を果たすことが明らかになってきており注目を集めている。しかしながら、好塩基球がどのように分化・成熟してくるのかについては不明な点が数多く残されている。申請者は、骨髄好塩基球中に未熟・成熟好塩基球に相当する2つの好塩基球分画を発見し、それら2つは機能的にも異なる性質を有していることを解明した。本研究では未熟好塩基球から成熟好塩基球への分化のメカニズムをRNAシーケンス解析などを用いて分子レベル・遺伝子レベルで解明し、好塩基球成熟を標的とした慢性アレルギー治療への応用を検討する。

Outline of Final Research Achievements

Basophils play critical roles in chronic allergic inflammation and the protective immunity against parasites. However, the developmental pathway of basophils remains elusive, especially at their final stage of differentiation. In this study, we assessed the differentiation trajectory of mouse basophils by virtue of single-cell RNA sequence analysis. Combining scRNA-seq analyses with flow-cytometric analyses, we identified immature-type basophils mainly reside in the bone marrow under homeostatic conditions. Immature basophils were characterized by their highly proliferative nature and differentiation capacity into mature basophils. Moreover, immature basophils displayed distinct activation properties with mature ones. Thus, the present study identified immature-type basophils which show distinctive proliferation and activation properties to mature ones.

Academic Significance and Societal Importance of the Research Achievements

好塩基球の固有の機能は長年分かっていなかったが、最近になって好塩基球がアレルギー疾患や寄生虫感染の治療標的となりうる可能性が浮上している。しかしながら、好塩基球の分化経路、特に分化の最終過程についてはほとんど明らかになっていない。本研究により、未熟好塩基球が新たに同定され、さらに未熟好塩基球の成熟メカニズムの一端が解明された。本研究成果は、アレルギー治療や寄生虫感染治療にも活かすことがでると考えられ、学術・社会的な面からも非常に意義のある研究である。

Research Products

• [Journal Article] 【ファゴサイトーシスとトロゴサイトーシス】免疫細胞におけるトロゴサイトーシスの役割 (2022)
  • Author(s): 三宅 健介, 烏山 一
  • Journal Title: 臨床免疫・アレルギー科. Volume: 77 Pages: 168-175
• [Journal Article] 【肺免疫から肺疾患を考える】アレルギー疾患や寄生虫感染症における好塩基球の役割 (2022)
  • Author(s): 三宅 健介, 烏山 一
  • Journal Title: 呼吸器内科 Volume: 40 Pages: 535-542
• [Journal Article] The Role of Trogocytosis in the Modulation of Immune Cell Functions (2021)
  • Author(s): Miyake Kensuke、Karasuyama Hajime
  • Journal Title: Cells Volume: 10 Issue: 5 Pages: 1255-1255
  • DOI: 10.3390/cells10051255
  • Peer Reviewed / Open Access
• [Journal Article] Basophils, a neglected minority in the immune system, have come into the limelight at last (2021)
  • Author(s): Karasuyama Hajime、Shibata Sho、Yoshikawa Soichiro、Miyake Kensuke
  • Journal Title: International Immunology Volume: 33 Issue: 12 Pages: 809-813
  • DOI: 10.1093/intimm/dxab021
  • Peer Reviewed
• [Journal Article] いま知りたい!!かじる?呑み込む?貪食の多様性 トロゴサイトーシスとエフェロサイトーシス トロゴサイトーシスによる免疫細胞機能の調節 (2021)
  • Author(s): 三宅 健介, 烏山 一.
  • Journal Title: 実験医学 Volume: 39 Pages: 2229-2232
• [Journal Article] E-cadherin is regulated by GATA-2 and marks the early commitment of mouse hematopoietic progenitors to the basophil and mast cell fates (2021)
  • Author(s): Wanet, A., Bassal, M. A., Patel, S. B., Marchi, F., Mariani, S. A., Ahmed, N., Zhang, H., Borchiellini, M., Chen, S., Zhang, J., Di Ruscio, A., Miyake, K., Tsai, M., Paranjape, A., Park, S. Y., Karasuyama, H., Schroeder, T., Dzierzak, E., Galli, S. J., Tenen, D. G., Welner, R. S.
  • Journal Title: Science Immunology Volume: 6 Issue: 56
  • DOI: 10.1126/sciimmunol.aba0178
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] アレルギー炎症における好塩基球の役割 (2021)
  • Author(s): 三宅 健介、烏山 一
  • Journal Title: アレルギーの臨床 Volume: 41 Pages: 25-28
• [Journal Article] 好塩基球の分化および活性化による2型免疫反応 (2021)
  • Author(s): 三宅 健介、吉川 宗一郎、柴田 翔、烏山 一
  • Journal Title: 血液内科 Volume: 82 Pages: 54-61
• [Journal Article] Basophils and their effector molecules in allergic disorders (2020)
  • Author(s): Miyake Kensuke、Shibata Sho、Yoshikawa Soichiro、Karasuyama Hajime
  • Journal Title: Allergy Volume: - Issue: 6 Pages: 1693-1706
  • DOI: 10.1111/all.14662
  • Peer Reviewed / Open Access
• [Journal Article] Skin‐infiltrating basophils promote atopic dermatitis‐like inflammation via IL‐4 production in mice (2020)
  • Author(s): Yamanishi Yoshinori、Mogi Kotone、Takahashi Kazufusa、Miyake Kensuke、Yoshikawa Soichiro、Karasuyama Hajime
  • Journal Title: Allergy Volume: 75 Issue: 10 Pages: 2613-2622
  • DOI: 10.1111/all.14362
  • Peer Reviewed / Open Access
• [Journal Article] Immunobiology of Acquired Resistance to Ticks (2020)
  • Author(s): Karasuyama Hajime、Miyake Kensuke、Yoshikawa Soichiro
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 601504-601504
  • DOI: 10.3389/fimmu.2020.601504
  • Peer Reviewed / Open Access
• [Journal Article] The role of basophils in acquired protective immunity to tick infestation (2020)
  • Author(s): Yoshikawa Soichiro、Miyake Kensuke、Kamiya Atsunori、Karasuyama Hajime
  • Journal Title: Parasite Immunology Volume: - Issue: 5
  • DOI: 10.1111/pim.12804
  • NAID: 120006937520
  • Peer Reviewed / Open Access
• [Presentation] Basophils promote the generation of highly phagocytic M2 macrophages which dampen excess inflammation at the resolution phase of allergic inflammation. (2021)
  • Author(s): Miyake K. Takahashi K, Ito J, Nakabayashi J, Shichino S, Yoshikawa S, Karasuyama H..
  • Organizer: 50th Annual Meeting of Japanese Society for Immunology
• [Presentation] Basophil dynamics during the activate phase of urticaria using an Oxazolone-induced contact hypersensitivity mouse model (2021)
  • Author(s): Ma N, Kishimoto I, Kambe N, Nakashima C, Otsuka A, Miyake K, Karasuyama H, Tanizaki H.
  • Organizer: 50th Annual Meeting of Japanese Society for Immunology
• [Presentation] Single-cell RNA-seq analysis provides novel insights into the mechanism underlying the termination of basophil-elicited allergic inflammation in the skin. (2021)
  • Author(s): Miyake K
  • Organizer: 50th Annual Meeting of Japanese Society for Immunology
  • Invited
• [Presentation] Chronic psychological stress exacerbates IgE-dependent chronic allergic inflammation via symphathetic nerve. (2021)
  • Author(s): Urakami H, Fujita Y, Komura A, Nagao K, Okutani R, Miyake K, Karasuyama H, Yoshikawa S.
  • Organizer: 50th Annual Meeting of Japanese Society for Immunology
• [Presentation] Sphingosine kinase 1 contributes to IgE-dependent basophil activation and the development of basophil-dependent delayed-onset skin allergic inflammation. (2021)
  • Author(s): Takahashi K, Miyake K, Karasuyama H.
  • Organizer: 50th Annual Meeting of Japanese Society for Immunology
• [Presentation] Single-cell RNA-seq analysis identified a novel subpopulation of basophils with immature phenotypes and unique functionality. (2021)
  • Author(s): Ito J, Miyake K, Nakabayashi J, Shichino S, Karasuyama H.
  • Organizer: 50th Annual Meeting of Japanese Society for Immunology
• [Presentation] Basophils gain the capacity of antigen presentation via trogocytosis-mediated transfer of peptide-MHC class II complexes from DCs (2021)
  • Author(s): Miyake K, Karasuyama H.
  • Organizer: 第44回日本分子生物学会年会（MBSJ2021）
• [Presentation] Basophil-derived IL-4 induces the generation of M2 macrophages which dampen skin chronic allergic inflammation via the efferocytic clearance of dead cells. (2021)
  • Author(s): Kensuke Miyake、Kazufusa Takahashi、Junya Ito、Jun Nakabayashi、Shigeyuki Shichino、Soichiro Yoshikawa、Hajime Karasuyama.
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] 好塩基球由来IL-4はマクロファージのCCL24産生を促し，好酸球浸潤を誘導する (2021)
  • Author(s): 高橋 和総、三宅 健介、須田 真未、大橋 健一、烏山 一
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] 熟好塩基球とは異なる活性化能を呈する未熟好塩基球の新規同定. (2021)
  • Author(s): 伊藤 潤哉、三宅 健介、中林 潤、七野 成之、烏山 一.
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] マウス，ヒトにおいて好中球エラスターゼは好塩基球からのIL-4分泌を促進する. (2021)
  • Author(s): 柴田 翔、三宅 健介、立石 知也、烏山 一、宮崎 泰成.
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] 麻疹の活動期に見られる好塩基球減少に関する動物モデルからの検証. (2021)
  • Author(s): 岸本 泉、馬 尼、谷崎 英昭、中嶋 千紗、大塚 篤司、三宅 健介、烏山 一、神戸 直智
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] Identification of two distinct subpopulations among basophils in the bone marrow (2020)
  • Author(s): Junya Ito, Kensuke Miyake, Shigeyuki Shichino, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: JSA/WAO Joint Congress 2020
  • Int'l Joint Research
• [Presentation] Monocyte-derived M2-like macrophages induced by activated basophils dampen IL-1α-mediated aggravation of allergic inflammation (2020)
  • Author(s): Kensuke Miyake, Junya Ito, Kazufusa Takahashi, Soichiro Yoshikawa, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: JSA/WAO Joint Congress 2020
  • Int'l Joint Research
• [Presentation] Basophils present antigens to T cells via trogocytosis-mediated acquisition of MHC class II (2020)
  • Author(s): Kensuke Miyake, Hajime Karasuyama.
  • Organizer: 第43回日本分子生物学会年会（MBSJ2020）