Galectin-9 signaling prolongs survival in murine lung-cancer by inducing macrophages to differentiate into plasmacytoid dendritic cell-like macrophages

Clin Immunol. 2012 Mar;142(3):296-307. doi: 10.1016/j.clim.2011.11.006. Epub 2011 Nov 25.


Galectin-9 (Gal-9) expanded plasmacytoid dendritic cell-like macrophages (pDC-Mϕs) in lung cancer-bearing mice and prolonged the survival. Gal-9 increased the frequency of CD11c(high) cells in M-CSF- but not GM-CSF-induced Mϕs in vitro in a Tim-3 independent manner. CD11c(high) cells differentiated with M-CSF+Gal-9 expressed pDC-Mϕ markers, such as PDCA-1 and F4/80. These cells expressed high TLR7, TLR8 and TLR9, although they exhibited decreased IFN-α mRNA levels. LPS or LLC stimulation further elevated pDC-Mϕ markers, indicating that M-CSF+Gal-9-induced Mϕs were pDC-Mϕ precursors. Moreover, LPS stimulation resulted in the increased IRF7 and E2-2 levels, suggesting that the pDC-Mϕ precursors matured into pDC-Mϕs. These matured pDC-Mϕs augmented NK cell-mediated cytotoxicity though they did not produce IFN-α upon TLR7 or TLR9 stimulation. The present results suggest that Gal-9 induces Mϕs to differentiate to pDC-Mϕs, and that this switch in differentiation favors the activation of NK cells that are able to prolong the survival of tumor-bearing mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Line
  • Cell Survival
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • Galectins / immunology*
  • Galectins / metabolism
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Macrophages / cytology*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Signal Transduction*


  • Galectins