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

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, Shigeru Chiba and Robert S. Negrin ()
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Antonio Pierini: Stanford University
Hidekazu Nishikii: Stanford University
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

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15068

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