Galectin-9 Increases Tim-3+ Dendritic Cells and CD8+ T Cells and Enhances Antitumor Immunity via Galectin-9-Tim-3 Interactions

Nagahara, Keiko; Arikawa, Tomohiro; Oomizu, Souichi; Kontani, Keiichi; Nobumoto, Atsuya; Tateno, Hiroaki; Watanabe, Kota; Niki, Toshiro; Katoh, Shigeki; Miyake, Minoru; Nagahata, Syun-Ichiro; Hirabayashi, Jun; Kuchroo, Vijay K.; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.4049/jimmunol.181.11.7660

Cited by 177 publications

(159 citation statements)

References 85 publications

(80 reference statements)

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“…The interaction of Tim3 with galectin-9 enhances anti-tumor immunity and prolongs the survival of tumor-bearing mice [21]. Nasopharyngeal tumors secrete exosomes containing galectin-9, which have been implicated in immune escape by the tumor through the induction of tumor-specific Tim3 + T-cell death [22].…”

Section: Discussionmentioning

confidence: 99%

The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine

Lee

Woo

Heo

et al. 2010

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 99%

The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine

Lee

Woo

Heo

et al. 2010

Biochemical and Biophysical Research Communications

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“…33 Tim-3 has been shown to be a negative mediator of not only adaptive immunity but also of innate immunity. 34 …”

Section: Discussionmentioning

confidence: 99%

The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal–fetal interface in early pregnancy

et al. 2015

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Decidual natural killer (dNK) cells actively participate in the establishment and maintenance of maternal-fetal immune tolerance and act as local guardians against infection. However, how dNK cells maintain the immune balance between tolerance and anti-infection immune responses during pregnancy remains unknown. Here, we demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) are expressed on over 60% of dNK cells. Tim-3 1 dNK cells display higher interleukin (IL)-4 and lower tumor necrosis factor (TNF)-a and perforin production. Human trophoblast cells can induce the transformation of peripheral NK cells into a dNK-like phenotype via the secretion of galectin-9 (Gal-9) and the interaction between Gal-9 and Tim-3. In addition, trophoblasts inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokine and perforin production by dNK cells, which can be attenuated by Tim-3 neutralizing antibodies. Interestingly, a decreased percentage of Tim-3-expressing dNK cells were observed in human miscarriages and murine abortion-prone models. Moreover, T helper (Th)2-type cytokines were decreased and Th1-type cytokines were increased in Tim-3 1 but not Tim-3 2 dNK cells from human and mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is important for the regulation of dNK cell function, which is beneficial for the maintenance of a normal pregnancy.

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“…4A). To determine whether IL-8 production was due to a TIM-3 signaling on galectin-9 ligation, we exposed cells to galectin-9 pretreated with lactose (30 mM) or rhTIM-3 (100 ng/ml), which has been shown to prevent galectin-9 binding to TIM-3 (46). Blockade of the TIM-3-galectin-9 interaction by lactose or rhTIM-3 suppressed IL-8 production in CFBE cells (Fig.…”

Section: Galectin-9 Induces Il-8 Production Via Tim-3 In Cfbe Cellsmentioning

confidence: 99%

Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways

Vega-Carrascal

Reeves

Niki

et al. 2011

The Journal of Immunology

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The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.

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Galectin-9 Increases Tim-3+ Dendritic Cells and CD8+ T Cells and Enhances Antitumor Immunity via Galectin-9-Tim-3 Interactions

Cited by 177 publications

References 85 publications

The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine

The inhibition of the T-cell immunoglobulin and mucin domain 3 (Tim3) pathway enhances the efficacy of tumor vaccine

The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal–fetal interface in early pregnancy

Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways

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