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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 54; no. 9; pp. 1419 - 1433
• Main Authors: Wen, Qi, Kong, Yuan, Zhao, Hong-Yan, Zhang, Yuan-Yuan, Han, Ting-Ting, Wang, Yu, Xu, Lan-Ping, Zhang, Xiao-Hui, Huang, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2019; Nature Publishing Group
• Subjects: 13; 13/31; 692/308/575; 692/699/1541/1990; Allografts; Bone marrow; Bone marrow transplantation; Care and treatment; Cell Biology; Colony-stimulating factor; Cytokines; Donors; Graft versus host reaction; Grafting; Grafts; Granulocyte colony-stimulating factor; Hematology; Hematopoietic stem cells; Homeostasis; Immune system; Inflammation; Internal Medicine; Leukocyte migration; Leukocytes (granulocytic); Lymphocytes T; Macrophages; Medicine; Medicine & Public Health; Pathogenesis; Peripheral blood; Phagocytosis; Prevention; Public Health; Risk factors; Stem cell transplantation; Stem Cells; Transplantation
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-019-0449-9

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.