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2023 Fiscal Year Annual Research Report

Deciphering regulatory mechanism of trained immunity in aged HSCs and clonal hematopoiesis of indeterminate potential (CHIP)

Research Project

Project/Area Number 22K16302
Research InstitutionKobe University

Principal Investigator

Afroj Tania  神戸大学, 医学研究科, 学術研究員 (50913034)

Project Period (FY) 2022-04-01 – 2024-03-31
KeywordsTrained immunity / Humanized mice / Hematopoietic stem cells / Aging
Outline of Annual Research Achievements

In the original research proposal, the objective was to investigate the functional impact of induced trained immunity in aged hematopoietic stem cells (HSCs) and its role in the pathogenesis of clonal hematopoiesis of indeterminate potential (CHIP).
In the FY2023, significant progress was made towards this goal. Specifically, a highly specialized humanized mouse model was established, demonstrating robust engraftment of human hematopoietic stem cells (HSCs). These human cells not only populated the bone marrow but also migrated to peripheral blood and organs such as the spleen. To assess the potential for developing CHIP compatibility, we examined the development of xenograft tumors, both hematological and solid, in this mouse model, showed pronounced infiltration of human myeloid cells within the tumor microenvironment. Myeloid cells have been identified as key mediators in transmitting trained immune responses from HSCs. Therefore, the focus shifted towards elucidating the role of human myeloid cells, particularly macrophages derived from CD34+ HSCs, within this context. Current investigations are ongoing on inducing trained immunity in macrophages through treatment with immune modulatory reagents. These treatments are administered to CD34+ HSCs within aged-humanized mice, mimicking conditions reflective of human aging. Targeting macrophages, pivotal players in the immune response, is anticipated to yield deeper insights into immune training mechanisms.

  • Research Products

    (4 results)

All 2023

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Open Access: 3 results) Presentation (1 results)

  • [Journal Article] Preclinical evaluation of the efficacy of an antibody to human SIRPα for cancer immunotherapy in humanized mouse models2023

    • Author(s)
      Saito Yasuyuki、Iida-Norita Rie、Afroj Tania、Refaat Alaa、Hazama Daisuke、Komori Satomi、Ohata Shinya、Takai Tomoko、Oduori Okechi S.、Kotani Takenori、Funakoshi Yohei、Koma Yu-Ichiro、Murata Yoji、Yakushijin Kimikazu、Matsuoka Hiroshi、Minami Hironobu、Yokozaki Hiroshi、Manz Markus G.、Matozaki Takashi
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1294814

    • DOI

      10.3389/fimmu.2023.1294814

    • Open Access / Int'l Joint Research
  • [Journal Article] CD47 promotes peripheral T cell survival by preventing dendritic cell mediated T cell necroptosis2023

    • Author(s)
      Komori Satomi、Saito Yasuyuki、Nishimura Taichi、Respatika Datu、Endoh Hiromi、Yoshida Hiroki、Sugihara Risa、Iida-Norita Rie、Afroj Tania、Takai Tomoko、Oduori Okechi S.、Nitta Eriko、Kotani Takenori、Murata Yoji、Kaneko Yoriaki、Nitta Ryo、Ohnishi Hiroshi、Matozaki Takashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Pages: p.e2304943120

    • DOI

      10.1073/pnas.2304943120

    • Open Access / Int'l Joint Research
  • [Journal Article] Identification of fibrocyte cluster in tumors reveals the role in antitumor immunity by PD-L1 blockade2023

    • Author(s)
      Mitsuhashi Atsushi、Koyama Kazuya、Ogino Hirokazu、Afroj Tania、Nguyen Na Thi、Yoneda Hiroto、Otsuka Kenji、Sugimoto Masamichi、Kondoh Osamu、Nokihara Hiroshi、Hanibuchi Masaki、Takizawa Hiromitsu、Shinohara Tsutomu、Nishioka Yasuhiko
    • Journal Title

      Cell Reports

      Volume: 42 Pages: 112162~112162

    • DOI

      10.1016/j.celrep.2023.112162

    • Open Access
  • [Presentation] Development of a novel cancer immunotherapy model targeting human macrophages2023

    • Author(s)
      Tania Afroj, Yasuyuki Saito, Satomi Komori, Tomoko Takai, Okechi S. Oduori, Takenori Kotani, Yoji Murata, and Takashi Matozaki
    • Organizer
      第21回生体機能研究会

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Published: 2024-12-25  

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