IL-3 and CSF-1 interact to promote generation of CD11c+ IL-10-producing macrophages

Unraveling the mechanisms of hematopoiesis regulated by multiple cytokines remains a challenge in hematology. IL-3 is an allergic cytokine with the multilineage potential, while CSF-1 is produced in the steady state with restricted lineage coverage. Here, we uncovered an instructive role of CSF-1 in...

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Bibliographic Details
Published in:PloS one 2014-04, Vol.9 (4), p.e95208-e95208
Main Authors: Sheng, Kuo-Ching, Herrero, Lara J, Taylor, Adam, Hapel, Andrew J, Mahalingam, Suresh
Format: Article
Language:English
Subjects:
Animals
Biology and Life Sciences
Blood
Bone marrow
c-Fos protein
CD11c antigen
CD11c Antigen - immunology
Cytokines
Cytology
Dendritic cells
Endocytosis
Fos protein
Gene expression
Hematology
Hematopoiesis
Immunology
Interleukin 1
Interleukin 10
Interleukin 3
Interleukin 6
Interleukin-1 - immunology
Interleukin-10 - immunology
Interleukin-3 - immunology
Interleukin-6 - immunology
Kinases
Lipopolysaccharides
Lymphocytes
Lymphocytes T
Macrophage colony-stimulating factor
Macrophage Colony-Stimulating Factor - immunology
Macrophages
Macrophages - cytology
Macrophages - immunology
Medical research
Mice
Mice, Inbred BALB C
Morphology
Myelopoiesis - immunology
R&D
Research & development
Stimulators
Tumor Necrosis Factor-alpha - immunology
Tumor necrosis factor-α
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Summary:Unraveling the mechanisms of hematopoiesis regulated by multiple cytokines remains a challenge in hematology. IL-3 is an allergic cytokine with the multilineage potential, while CSF-1 is produced in the steady state with restricted lineage coverage. Here, we uncovered an instructive role of CSF-1 in IL-3-mediated hematopoiesis. CSF-1 significantly promoted IL-3-driven CD11c+ cell expansion and dampened basophil and mast cell generation from C57BL/6 bone marrow. Further studies indicated that the CSF-1/CSF-1R axis contributed significantly to IL-3-induced CD11c+ cell generation through enhancing c-Fos-associated monopoiesis. CD11c+ cells induced by IL-3 or IL-3/CSF-1 were competent in cellular maturation and endocytosis. Both IL-3 and IL-3/CSF-1 cells lacked classical dendritic cell appearance and resembled macrophages in morphology. Both populations produced a high level of IL-10, in addition to IL-1, IL-6 and TNFα, in response to LPS, and were relatively poor T cell stimulators. Collectively, these findings reveal a role for CSF-1 in mediating the IL-3 hematopoietic pathway through monopoiesis, which regulates expansion of CD11c+ macrophages.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0095208