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Foxp3+ regulatory T cells maintain the bone marrow microenvironment for B cell lymphopoiesis

Author

Listed:
  • Antonio Pierini

    (Stanford University
    Hematopoietic Stem Cell Transplantation Program, University of Perugia, Piazzale Menghini, 06132, Sant’Andrea delle Fratte)

  • Hidekazu Nishikii

    (Stanford University
    Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai)

  • Jeanette Baker

    (Stanford University)

  • Takaharu Kimura

    (Stanford University of Medicine)

  • Hye-Sook Kwon

    (Stanford University)

  • Yuqiong Pan

    (Stanford University)

  • Yan Chen

    (Stanford University)

  • Maite Alvarez

    (Stanford University)

  • William Strober

    (Stanford University)

  • Andrea Velardi

    (Hematopoietic Stem Cell Transplantation Program, University of Perugia, Piazzale Menghini, 06132, Sant’Andrea delle Fratte)

  • Judith A. Shizuru

    (Stanford University)

  • Joy Y. Wu

    (Stanford University of Medicine)

  • Shigeru Chiba

    (Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai)

  • Robert S. Negrin

    (Stanford University)

Abstract

Foxp3+ regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients. Treg cells can control physiological IL-7 production that is indispensable for normal B-cell lymphopoiesis and is mainly sustained by a subpopulation of ICAM1+ perivascular stromal cells. Our study demonstrates that Treg cells are important for B-cell differentiation from HSCs by maintaining immunological homoeostasis in the bone marrow microenvironment, both in physiological conditions and after bone marrow transplantation.

Suggested Citation

  • Antonio Pierini & Hidekazu Nishikii & Jeanette Baker & Takaharu Kimura & Hye-Sook Kwon & Yuqiong Pan & Yan Chen & Maite Alvarez & William Strober & Andrea Velardi & Judith A. Shizuru & Joy Y. Wu & Shi, 2017. "Foxp3+ regulatory T cells maintain the bone marrow microenvironment for B cell lymphopoiesis," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15068
    DOI: 10.1038/ncomms15068
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