Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner

Oomizu, Souichi; Arikawa, Tomohiro; Niki, Toshiro; Kadowaki, Takeshi; Ueno, Masaki; Nishi, Nozomu; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.1016/j.clim.2012.01.004

Cited by 111 publications

(97 citation statements)

References 35 publications

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“…Several studies have shown Tim-3-independent immune cell regulation by Gal-9 (7,11,13,24,25), indicating that other pathways are involved in Gal-9 modulation of the immune response. Gal-9 binding to protein disulfide isomerase (PDI) on Th2 cells results in increased cell migration (7).…”

Section: Discussionmentioning

confidence: 99%

“…Originally described as an eosinophil chemoattractant, Gal-9 is now known to be an important pleiotropic immune modulator affecting numerous immune cell types (reviewed in references 8 and 9). Gal-9 is thought to be involved in the activation of innate immune responses (3,10) and the downregulation of Th17 (11) and Th1 responses (12,13). Gal-9 can promote inflammation through triggering proinflammatory cytokine production from monocytes (3) and inducing maturation of macrophages (14) and monocyte-derived dendritic cells (mDC) (10).…”

mentioning

confidence: 99%

“…Gal-9 binding to PDI on Th2 cells results in increased cell migration (7). Through interaction with an as-yet unidentified glycoprotein, the development of Th17 cells is inhibited in Gal-9 knockout (KO) mice (11). Gal-9 can induce the production of proinflammatory cytokines from Th cells in a manner that does not require Tim-3 (24).…”

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confidence: 99%

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Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice

Golden-Mason

McMahan

Strong³

et al. 2013

J Virol

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112

106

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h Galectin-9 is a pleiotropic immune modulator affecting numerous cell types of innate and adaptive immunity. Patients with chronic infection with either hepatitis C virus (HCV) or HIV have elevated circulating levels. Limited data exist on the regulation of natural killer (NK) cell function through interaction with galectin-9. We found that galectin-9 ligation downregulates multiple immune-activating genes, including eight involved in the NK cell-mediated cytotoxicity pathway, impairs lymphokine-activated killing, and decreases the proportion of gamma interferon (IFN-␥)-producing NK cells that had been stimulated with interleukin-12 (IL-12)/IL-15. We demonstrate that the transcriptional and functional changes induced by galectin-9 are independent of Tim-3. Consistent with these results for humans, we find that the genetic absence of galectin-9 in mice is associated with greater IFN-␥ production by NK cells and enhanced degranulation. We also show that in the setting of a short-term (4-day) murine cytomegalovirus infection, terminally differentiated NKs accumulate in the livers of galectin-9 knockout mice, and that hepatic NKs spontaneously produce significantly more IFN-␥ in this setting. Taken together, our results indicate that galectin-9 engagement impairs the function of NK cells, including cytotoxicity and cytokine production.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice

Golden-Mason

McMahan

Strong³

et al. 2013

J Virol

Self Cite

112

106

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“…NOZ cells (1.0x10 6 /dish) were seeded in 100-mm culture dishes and cultured for 24 or 48 h, then 0.3 µM Gal-9 was added. The cells were lysed using a protease inhibitor cocktail (Pro-Prep complete protease inhibitor mixture; iNtRON Biotechnology, Sungnam, Korea).…”

Section: Methodsmentioning

confidence: 99%

Galectin-9: An anticancer molecule for gallbladder carcinoma

Tadokoro

Morishita

Fujihara

et al. 2016

International Journal of Oncology

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Abstract. Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeattype galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.

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“…To date, Gal-9 is the only ligand for Tim-3 which has been identified. In contrast, Oomizu et al [31] showed that Gal-9 can inhibit Th17 cell differentiation through an IL-2-dependent pathway, but a Tim-3-independent pathway. Moreover, recent studies have revealed potential ligands for TIM-3, including phosphatidylserine and carbohydrate [7].…”

Section: Introductionmentioning

confidence: 92%

T cell immunoglobulin-3 as a new therapeutic target for rheumatoid arthritis

Zhao

et al. 2012

Expert Opinion on Therapeutic Targets

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Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner

Cited by 111 publications

References 35 publications

Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice

Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice

Galectin-9: An anticancer molecule for gallbladder carcinoma

T cell immunoglobulin-3 as a new therapeutic target for rheumatoid arthritis

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