title: Granulocyte Colony-Stimulating Factor Induces Osteoblast Inhibition by B Lymphocytes and Osteoclast Activation by T Lymphocytes during Hematopoietic Stem/Progenitor Cell Mobilization.
abstract: In the bone marrow (BM), hematopoietic stem and progenitor cells (HSPCs) reside in specialized niches near osteoblast cells at the endosteum. HSPCs that egress to peripheral blood are widely used for transplant, and mobilization is most commonly performed with recombinant human granulocyte colony-stimulating factor (G-CSF). However, the cellular targets of G-CSF that initiate the mobilization cascade and bone remodeling are not completely understood. Here, we examined whether T and B lymphocytes modulate the bone niche and influence HSPC mobilization. We used T and B defective mice to show that G-CSF-induced mobilization of HSPCs correlated with B lymphocytes but poorly with T lymphocytes. In addition, we found that defective B lymphocytes prevent G-CSF-mediated osteoblast disruption, and further study showed BM osteoblasts were reduced coincident with mobilization, induced by elevated expression of dickkopf1 of BM B lymphocytes. BM T cells were also involved in G-CSF-induced osteoclast activation by regulating the Receptor Activator of Nuclear Factor-κ B Ligand/Osteoprotegerin (RANKL/OPG) axis. These data provide evidence that BM B and T lymphocytes play a role in G-CSF-induced HSPC mobilization by regulating bone remodeling.
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics, Ministry of Education; Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China; State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Sidan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China.
authors.forename: Tianshou
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of Beijing Military Area Command, Beijing, China.
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China.
authors.forename: Yinchao
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Lanting
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China. Electronic address: liqiaochuan@sohu.com.
authors.forename: Qiaochuan
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China.
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Hematopoietic stem/progenitor cells; Lymphocyte; Stem cell niche