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

Kadowaki, Takeshi; Arikawa, Tomohiro; Shinonaga, Rika; Oomizu, Souichi; Inagawa, Hiroyuki; Soma, Gen‐Ichiro; Niki, Toshiro; Hirashima, Mitsuomi

doi:10.1016/j.clim.2011.11.006

Cited by 37 publications

(30 citation statements)

References 47 publications

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“…HMGB1 is a macrophage-derived late proinflammatory cytokine, and TLR4 and CD14 are required for the release of HMGB1 [50]. pDC-like macrophages suppress LPS-induced release of early proinflammatory cytokines from macrophages by suppressing TLR4 and CD14 expression on macrophages [21,22]. Thus, it was suggested that immunosuppressive pDC-like macrophages may mediate decreased release of early and late proinflammatory cytokines from macrophages that also, at least in part, may be involved in the prolongation of survival seen in these experiments.…”

Section: Resultsmentioning

confidence: 99%

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+macrophages

et al. 2013

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IntroductionGalectin-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.MethodsWe 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.ResultsGalectin-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.ConclusionThese 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.

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Section: Resultsmentioning

confidence: 99%

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+macrophages

et al. 2013

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“…It has been proposed that both attachment and invasion of tumour cells are inhibited by Gal-9 through interference with cell adhesion molecules binding to ligands on the vascular endothelium and the extracellular matrix [36]. Treating with recombinant Gal-9 was shown to decrease metastasis of cancer in several studies [37-39]. Nevertheless, Irie et al., reported that overexpression of Gal-9 in breast cancer cells exhibited a reduced adhesion to the extracellular matrix [20].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of High Gal-9 Expression in Solid Tumours: a Meta-Analysis

Wang

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recently, many studies have demonstrated that galectin-9 (Gal-9) exhibits altered expression and has a close association with metastasis and recurrence in various cancers. Therefore, we conducted a meta-analysis to assess the prognostic role of Gal-9 expression in solid tumours. Methods: We searched PubMed, Embase, and Web of Science until June 2017 and identified fourteen eligible studies containing 2,408 patients to include in the meta-analysis. Results: The pooled results indicated that higher Gal-9 expression in cancer tissue associated with an improved CSS (HR=0.48, 95% CI 0.39-0.58). In the subgroup analysis, a significant relationship was observed between higher Gal-9 expression and both CSS (HR=0.48, 95% CI 0.39-0.59) and OS (HR=0.62, 95% CI 0.49-0.78) in digestive cancers. Conclusions: The findings of this meta-analysis highlight the role of Gal-9 as a useful clinical prognostic biomarker, which may facilitate the treatment of patients with solid tumours.

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“…Yang et al also showed that galectin-9 expression was significantly decreased in gastric cancer tissues, and LNM and survival rate were found to be associated with galectin-9 expression, but no correlation was found between galectin-9 expression and Tim-3 in gastric cancer [36]. It has been also shown that galectin-9 signaling can prolong survival in murine lung-cancer by inducing macrophage to differentiate into plasmacytoid dendritic cell-like macrophages [37]. Our results and previous reports suggest that galectin-9 might be a possible suppressor for tumor, and Tim-3-regulated activity of peripheral NK cells in lung adenocarcinoma might not be mediated by Tim-3-galectin-9 pathway.…”

Section: Discussionmentioning

confidence: 99%

Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma

Huang

Tan

et al. 2015

International Immunopharmacology

177

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

Cited by 37 publications

References 47 publications

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+macrophages

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+macrophages

Prognostic Role of High Gal-9 Expression in Solid Tumours: a Meta-Analysis

Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma

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