title: Galectin-9 signaling prolongs survival in murine lung-cancer by inducing macrophages to differentiate into plasmacytoid dendritic cell-like macrophages.
abstract: 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.
authors.affiliation: Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arikawa
authors.forename: Rika
authors.initials: R
authors.lastname: Shinonaga
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inagawa
authors.forename: Genichiro
authors.initials: G
authors.lastname: Soma
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D037161:Galectins / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D037161:Galectins