title: Galectin-9 prolongs the survival of septic mice by expanding Tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages.
abstract: BACKGROUND
  Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed.
  
  
  METHODS
  We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells.
  
  
  RESULTS
  Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1+ CD11c+ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, γδT cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3+ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1+ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1+ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17+ NK1.1+ NKT cells.
  
  
  CONCLUSIONS
  These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines.
authors: Takashi
authors: T
authors: Kadowaki
authors: Asahiro
authors: A
authors: Morishita
authors: Toshiro
authors: T
authors: Niki
authors: Junko
authors: J
authors: Hara
authors: Miwa
authors: M
authors: Sato
authors: Joji
authors: J
authors: Tani
authors: Hisaaki
authors: H
authors: Miyoshi
authors: Hirohito
authors: H
authors: Yoneyama
authors: Tsutomu
authors: T
authors: Masaki
authors: Toshio
authors: T
authors: Hattori
authors: Akihiro
authors: A
authors: Matsukawa
authors: Mitsuomi
authors: M
authors: Hirashima
mesh_terms: D000818:Animals; D017209:Apoptosis; D039521:CD11c Antigen / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D037161:Galectins / Q000627:therapeutic use*; D000072597:Hepatitis A Virus Cellular Receptor 2; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D037161:Galectins; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus; C442241:Havcr2 protein, mouse; C508186:galectin 9, mouse