title: Galectin-9 attenuates acute lung injury by expanding CD14- plasmacytoid dendritic cell-like macrophages.
abstract: BACKGROUND
  Galectin (Gal)-9 plays a crucial role in the modulation of innate and adaptive immunity.
  
  
  OBJECTIVE
  To investigate whether Gal-9 plays a role in a murine acute lung injury (ALI) model.
  
  
  METHODS
  C57BL/6 mice were pretreated with Gal-9 by subcutaneous injection 24 and 48 hours before intranasal LPS inoculation.
  
  
  RESULTS
  Gal-9 suppressed pathological changes of ALI induced by LPS. Gal-9 reduced levels of proinflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and keratinocyte-derived cytokine; decreased neutrophils; and increased IL-10 and CD11b(+)Gr-1(+) macrophages in the bronchoalveolar lavage fluid of ALI mice. In Gal-9-deficient mice, pathological changes of ALI were exaggerated, and the number of neutrophils and the TNF-α level were increased. CD11b(+)Gr-1(+) cells were increased in the spleen of both Gal-9-treated and phosphate-buffered saline (PBS)-treated ALI mice, but only Gal-9 increased the ability of CCR2-expressing macrophages to migrate toward monocyte chemoattractant protein-1. Transfer of CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated mice ameliorated ALI. CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated but not PBS-treated mice suppressed TNF-α and keratinocyte-derived cytokine production from LPS-stimulated macrophages, and down-regulated Toll-like receptor-4 (TLR4) and TLR2 expression on thioglycollate-elicited macrophages. Fluorescence-activated cell-sorting analysis revealed that CD14 is negligible on CD11b(+)Gr-1(+) macrophages obtained from Gal-9-treated mice, although those from both groups resembled plasmacytoid dendritic cells (pDCs). Gal-9 down-regulated CD14 on pDC-like macrophages from PBS-treated mice independently of Gal-9/Tim-3 (T-cell immunoglobulin- and mucin domain-containing molecule-3) interaction, resulting in the acquisition of suppressive function, suggesting that the loss of CD14 by Gal-9 is critical for the suppression of pDC-like macrophages.
  
  
  CONCLUSIONS
  Gal-9 attenuates ALI by expanding CD14(-)CD11b(+)Gr-1(+) pDC-like macrophages by preferentially suppressing macrophage functions to release proinflammatory cytokines through TLR4 and TLR2 down-regulation.
authors.affiliation: Department of Respiratory Medicine, Faculty of Life Science, Kumamoto University, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kojima
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Saita
authors.forename: Eisuke
authors.initials: E
authors.lastname: Goto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Tsumura
authors.forename: Reina
authors.initials: R
authors.lastname: Tanaka
authors.forename: Aiko
authors.initials: A
authors.lastname: Masunaga
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kohrogi
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D037161:Galectins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007113:Immunity, Innate; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D037161:Galectins; D008070:Lipopolysaccharides; C508186:galectin 9, mouse