TY - JOUR
T1 - Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice
AU - Day, Ryan B.
AU - Bhattacharya, Deepta
AU - Nagasawa, Takashi
AU - Link, Daniel C.
N1 - Funding Information:
The authors thank Dr David Rowe for the Col2.3gfp mice. This work was supported by National Institutes of Health (NIH) National Heart, Lung, and Blood Institute grants RO1 HL60772 (D.C.L.) and F30 HL112552-02 (R.B.D.) and NIH National Cancer Institute grant P50 CA171963 (D.C.L.). D.B. is a New York Stem Cell Foundation Robertson Investigator.
Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015
Y1 - 2015
N2 - The mechanisms that mediate the shift from lymphopoiesis to myelopoiesis in response to infectious stress are largely unknown. We show that treatment with granulocyte colonystimulating factor (G-CSF), which is often induced during infection, results in marked suppression of B lymphopoiesis at multiple stages of B-cell development. Mesenchymallineage stromal cells in the bone marrow, including CXCL12-abundant reticular (CAR) cells and osteoblasts, constitutively support B lymphopoiesis through the production of multiple B trophic factors. G-CSF acting through a monocytic cell intermediate reprograms these stromal cells, altering their capacity to support B lymphopoiesis. G-CSF treatment is associated with an expansion of CAR cells and a shift toward osteogenic lineage commitment. It markedly suppresses the production of multiple B-cell trophic factors by CAR cells and osteoblasts, including CXCL12, kit ligand, interleukin-6, interleukin-7, and insulin-like growth factor-1. Targeting bone marrow stromal cells is one mechanism by which inflammatory cytokines such as G-CSF actively suppress lymphopoiesis.
AB - The mechanisms that mediate the shift from lymphopoiesis to myelopoiesis in response to infectious stress are largely unknown. We show that treatment with granulocyte colonystimulating factor (G-CSF), which is often induced during infection, results in marked suppression of B lymphopoiesis at multiple stages of B-cell development. Mesenchymallineage stromal cells in the bone marrow, including CXCL12-abundant reticular (CAR) cells and osteoblasts, constitutively support B lymphopoiesis through the production of multiple B trophic factors. G-CSF acting through a monocytic cell intermediate reprograms these stromal cells, altering their capacity to support B lymphopoiesis. G-CSF treatment is associated with an expansion of CAR cells and a shift toward osteogenic lineage commitment. It markedly suppresses the production of multiple B-cell trophic factors by CAR cells and osteoblasts, including CXCL12, kit ligand, interleukin-6, interleukin-7, and insulin-like growth factor-1. Targeting bone marrow stromal cells is one mechanism by which inflammatory cytokines such as G-CSF actively suppress lymphopoiesis.
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U2 - 10.1182/blood-2015-02-629444
DO - 10.1182/blood-2015-02-629444
M3 - Article
C2 - 25814527
AN - SCOPUS:84944555458
SN - 0006-4971
VL - 125
SP - 3114
EP - 3117
JO - Blood
JF - Blood
IS - 20
ER -