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

222 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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