Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells

Suwen Wei, Sayan Nandi, Violeta Chitu, Yee Guide Yeung, Wenfeng Yu, Minmei Huang, Lewis T. Williams, Haishan Lin, E. Richard Stanley

Research output: Contribution to journalArticle

204 Citations (Scopus)

Abstract

CSF-1 is broadly expressed and regulates macrophage and osteoclast development. The action and expression of IL-34, a novel CSF-1R ligand, were investigated in the mouse. As expected, huIL-34 stimulated macrophage proliferation via the huCSF-1R, equivalently to huCSF-1, but was much less active at stimulating mouse macrophage proliferation than huCSF-1. Like muCSF-1, muIL-34 and a muIL-34 isoform lacking Q81 stimulated mouse macrophage proliferation, CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors. However, they respectively possessed twofold and fivefold lower affinities for the CSF-1R and correspondingly, lower activities than muCSF-1. Furthermore, muIL-34, when transgenically expressed in a CSF-1-dependent manner in vivo, rescued the bone, osteoclast, tissue macrophage, and fertility defects of Csf1op/op mice, suggesting similar regulation of CSF-1R-expressing cells by. IL-34 and CSF-1. Whole-mount IL34 in situ hybridization and CSF-1 reporter expression revealed that IL34 mRNA was strongly expressed in the embryonic brain at E11.5, prior to the expression of Csf1 mRNA. QRT-PCR revealed that compared with Csf1 mRNA, IL34 mRNA levels were lower in pregnant uterus and in cultured osteoblasts, higher in most regions of the brain and heart, and not compensatorily increased in Csf1op/op mouse tissues. Thus, the different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues.

Original languageEnglish (US)
Pages (from-to)495-505
Number of pages11
JournalJournal of Leukocyte Biology
Volume88
Issue number3
DOIs
StatePublished - Sep 2010

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Macrophage Colony-Stimulating Factor Receptors
Macrophage Colony-Stimulating Factor
Myeloid Cells
Macrophages
Osteoclasts
Messenger RNA
Brain
Osteoblasts
Uterus
In Situ Hybridization
Fertility
Tyrosine
Protein Isoforms
Phosphorylation
Cytokines
Ligands
Bone and Bones
Polymerase Chain Reaction

Keywords

  • Cytokines
  • Hematopoiesis
  • Inflammation
  • Macrophages
  • Osteoclasts
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. / Wei, Suwen; Nandi, Sayan; Chitu, Violeta; Yeung, Yee Guide; Yu, Wenfeng; Huang, Minmei; Williams, Lewis T.; Lin, Haishan; Stanley, E. Richard.

In: Journal of Leukocyte Biology, Vol. 88, No. 3, 09.2010, p. 495-505.

Research output: Contribution to journalArticle

Wei, Suwen ; Nandi, Sayan ; Chitu, Violeta ; Yeung, Yee Guide ; Yu, Wenfeng ; Huang, Minmei ; Williams, Lewis T. ; Lin, Haishan ; Stanley, E. Richard. / Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. In: Journal of Leukocyte Biology. 2010 ; Vol. 88, No. 3. pp. 495-505.
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AU - Wei, Suwen

AU - Nandi, Sayan

AU - Chitu, Violeta

AU - Yeung, Yee Guide

AU - Yu, Wenfeng

AU - Huang, Minmei

AU - Williams, Lewis T.

AU - Lin, Haishan

AU - Stanley, E. Richard

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N2 - CSF-1 is broadly expressed and regulates macrophage and osteoclast development. The action and expression of IL-34, a novel CSF-1R ligand, were investigated in the mouse. As expected, huIL-34 stimulated macrophage proliferation via the huCSF-1R, equivalently to huCSF-1, but was much less active at stimulating mouse macrophage proliferation than huCSF-1. Like muCSF-1, muIL-34 and a muIL-34 isoform lacking Q81 stimulated mouse macrophage proliferation, CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors. However, they respectively possessed twofold and fivefold lower affinities for the CSF-1R and correspondingly, lower activities than muCSF-1. Furthermore, muIL-34, when transgenically expressed in a CSF-1-dependent manner in vivo, rescued the bone, osteoclast, tissue macrophage, and fertility defects of Csf1op/op mice, suggesting similar regulation of CSF-1R-expressing cells by. IL-34 and CSF-1. Whole-mount IL34 in situ hybridization and CSF-1 reporter expression revealed that IL34 mRNA was strongly expressed in the embryonic brain at E11.5, prior to the expression of Csf1 mRNA. QRT-PCR revealed that compared with Csf1 mRNA, IL34 mRNA levels were lower in pregnant uterus and in cultured osteoblasts, higher in most regions of the brain and heart, and not compensatorily increased in Csf1op/op mouse tissues. Thus, the different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues.

AB - CSF-1 is broadly expressed and regulates macrophage and osteoclast development. The action and expression of IL-34, a novel CSF-1R ligand, were investigated in the mouse. As expected, huIL-34 stimulated macrophage proliferation via the huCSF-1R, equivalently to huCSF-1, but was much less active at stimulating mouse macrophage proliferation than huCSF-1. Like muCSF-1, muIL-34 and a muIL-34 isoform lacking Q81 stimulated mouse macrophage proliferation, CSF-1R tyrosine phosphorylation, and signaling and synergized with other cytokines to generate macrophages and osteoclasts from cultured progenitors. However, they respectively possessed twofold and fivefold lower affinities for the CSF-1R and correspondingly, lower activities than muCSF-1. Furthermore, muIL-34, when transgenically expressed in a CSF-1-dependent manner in vivo, rescued the bone, osteoclast, tissue macrophage, and fertility defects of Csf1op/op mice, suggesting similar regulation of CSF-1R-expressing cells by. IL-34 and CSF-1. Whole-mount IL34 in situ hybridization and CSF-1 reporter expression revealed that IL34 mRNA was strongly expressed in the embryonic brain at E11.5, prior to the expression of Csf1 mRNA. QRT-PCR revealed that compared with Csf1 mRNA, IL34 mRNA levels were lower in pregnant uterus and in cultured osteoblasts, higher in most regions of the brain and heart, and not compensatorily increased in Csf1op/op mouse tissues. Thus, the different spatiotemporal expression of IL-34 and CSF-1 allows for complementary activation of the CSF-1R in developing and adult tissues.

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KW - Hematopoiesis

KW - Inflammation

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KW - Osteoclasts

KW - Tumor-associated macrophages

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