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G-CSF-induced macrophage polarization and mobilization may prevent acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 54, pages 1419–1433 (2019)Cite this article

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Abstract

Macrophages (MΦs) are an important immune cell population that are essential for tissue homeostasis and disease pathogenesis. MΦs are now classified as either M1, which produce pro-inflammatory cytokines, or M2, which produce antiinflammatory cytokines. The impact of granulocyte colony-stimulating factor (G-CSF) on MΦs in humans is unclear. Moreover, little is known about the association between MΦ subsets in allografts and the occurrence of acute graft-versus-host disease (aGVHD) in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current study, we found that the M1/M2 ratio was markedly decreased in both G-CSF-treated bone marrow (post-BM) and G-CSF-treated peripheral blood from healthy donors. Post-BM MΦs exhibited reduced migration and increased phagocytosis. Moreover, post-BM MΦs reduced the percentage of Th1 and Tc1 lineages and increased the percentage of Th2, Tc2, and Treg lineages. Patients who received BM grafts with a higher M1/M2 ratio exhibited a higher incidence of grade 2–4 aGVHD. In summary, our data indicate that G-CSF decreases the M1/M2 ratio in BM grafts from healthy donors, which may contribute to preventing the occurrence of grade 2–4 aGVHD in patients after allo-HSCT.

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Acknowledgements

We thank all of the core facilities at Peking University Institute of Hematology for sample collection. This work was supported by the National Key Research and Development Program (2017YFA0104500), the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001), National Natural Science Foundation of China (grant nos. 81870139 & 81570127 & 81530046), Clinical Medicine Plus X - Young Scholars Project of Peking University, and the Science and Technology Project of Guangdong Province of China (2016B030230003). American Journal Experts (www.journalexperts.com) provided editorial assistance to the authors during the preparation of the manuscript.

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  1. These authors contributed equally: Qi Wen and Yuan Kong

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  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Beijing, China

    Qi Wen, Yuan Kong, Hong-Yan Zhao, Yuan-Yuan Zhang, Ting-Ting Han, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang & Xiao-Jun Huang

  2. Nanfang Hospital, Southern Medical University, Guangzhou, China

    Qi Wen & Xiao-Jun Huang

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Wen, Q., Kong, Y., Zhao, HY. et al. G-CSF-induced macrophage polarization and mobilization may prevent acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 54, 1419–1433 (2019). https://doi.org/10.1038/s41409-019-0449-9

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