Galectin-9 ameliorates immune complex-induced arthritis by regulating FcγR expression on macrophages

Arikawa, Tomohiro; Watanabe, Kota; Seki, Masako; Matsukawa, Akihiro; Oomizu, Souichi; Sakata, Kozue; Sakata, Atsuko; Ueno, Masaki; Saita, Naoki; Niki, Toshiro; Yamauchi, Akira; Hirashima, Mitsuomi

doi:10.1016/j.clim.2009.09.004

Cited by 51 publications

(52 citation statements)

References 31 publications

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“…Injected galectin-9 markedly suppressed bone destruction in arthritic rats without significant suppression of the inflammation. As galectin-9 is reported to suppress inflammation in arthritis, 27 failure in the significant suppression of inflammation could be attributed to the low dose of galectin-9 in our current experiments. However, the dose of galectin-9 injected to arthritic rats in our current experiments (5 mg per injection) efficiently inhibited bone destruction, possibly through inhibiting osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 62%

Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

Moriyama

Kukita

et al. 2014

Laboratory Investigation

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Galectins are a unique family of lectins bearing one or two carbohydrate recognition domains (CRDs) that have the ability to bind molecules with b-galactoside-containing carbohydrates. It has been shown that galectins regulate not only cell growth and differentiation but also immune responses, as well as inflammation. Galectin-9, a tandem repeat type of galectin, was originally identified as a chemotactic factor for eosinophils, and is also involved in the regulatory process of inflammation. Here, we examined the involvement of galectin-9 and its receptor, T-cell immunoglobulin-and mucin-domain-containing molecule 3 (Tim-3), in the control of osteoclastogenesis and inflammatory bone destruction. Expression of Tim-3 was detected in osteoclasts and its mononuclear precursors in vivo and in vitro. Galectin-9 markedly inhibited osteoclastogenesis as evaluated in osteoclast precursor cell line RAW-D cells and primary bone marrow cells of mice and rats. The inhibitory effects of galectin-9 on osteoclastogenesis was negated by the addition of b-lactose, an antagonist for galectin binding, suggesting that the inhibitory effect of galectin-9 was mediated through CRD. When galectin-9 was injected into rats with adjuvant-induced arthritis, marked suppression of bone destruction was observed. Inflammatory bone destruction could be efficiently ameliorated by controlling the Tim-3/galectin-9 system in rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 62%

Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

Moriyama

Kukita

et al. 2014

Laboratory Investigation

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“…As disease progresses, the presence of bacteria and LPS may amplify TIM-3-mediated neutrophil recruitment. Subsequently, on chronic inflammation and infection, the lack of TIM-3 and galectin-9 protein caused by proteolytic cleavage may result in a dysregulation of this signaling axis, which would then fail to terminate the inflammatory response because of lack of selective apoptosis of inflammatory immune cells (53), or expansion of immunosuppressive macrophages (34,41) or regulatory T cells (66). Indeed, disruption of this mechanism using TIM-3 or galectin-9 blocking Abs has been reported to result in increased neutrophil infiltration and tissue damage in a model of liver ischemia/reperfusion (31), experimental adhesion formation (30), and multiple sclerosis (32).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, disruption of this mechanism using TIM-3 or galectin-9 blocking Abs has been reported to result in increased neutrophil infiltration and tissue damage in a model of liver ischemia/reperfusion (31), experimental adhesion formation (30), and multiple sclerosis (32). Conversely, administration of proteolytically stable recombinant galectin-9 ameliorated symptoms in a model of arthritis (34,35,66), diabetes (67), and multiple sclerosis (32). Galectin-9 has also shown to exhibit a protective effect in lung infection in a mouse model of hypersensitivity pneumonitis induced by Trichosporon asahii (41).…”

Section: Discussionmentioning

confidence: 99%

“…Proteolytically stable human galectin-9 was a kind gift from GalPharma (Kagawa, Japan). Expression and purification of stable human galectin-9 was performed as previously described (34,35). In brief, galectins were expressed using the pET expression system (Novagen, Madison, WI) in Escherichia coli BL21 (DE3) and purified with a lactose-agarose column (Seikagaku Kogyo, Tokyo, Japan) and dialyzed against PBS.…”

Section: Abs and Recombinant Proteinsmentioning

confidence: 99%

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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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“…Studies in models of inflammatory disease, such as complex immune-induced arthritis, allergic asthma and diabetes, support an anti-inflammatory role for gal-9 [10][11][12]. Unlike gal-1, gal-3 can both positively and negatively regulate the inflammatory response, depending on factors such as the specific inflammatory conditions or the type of target cell [13].…”

Section: Introductionmentioning

confidence: 99%

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

Fuente

Pérez‐Gala

Bonay

et al. 2012

The Journal of Pathology

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2 ABSTRACT.We have investigated the expression and role of galectin-1 and other galectins in psoriasis and in the Th1/Th17 effector and dendritic cell responses associated with this chronic inflammatory skin condition. To determine differences between psoriasis patients and healthy donors, galectins expression was analyzed by RT-PCR assays in skin samples and specifically on epidermal and peripheral blood dendritic cells by immunofluorescence and flow cytometry.In skin of healthy donors galectins 1, 3 and 9 were expressed in a high proportion of Langerhans cells. Also, galectins were differentially expressed in peripheral blood dendritic cell subsets; galectin-1 and galectin-9 were highly expressed in peripheral myeloid dendritic cells compared with plasmacytoid dendritic cells. We found that non-lesional as well as lesional skin samples from psoriasis patients had low levels of galectin-1 at mRNA and protein level in parallel with low levels of IL-10 mRNA compared with skin from healthy patients. However, only lesional skin samples expressed high levels of

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Galectin-9 ameliorates immune complex-induced arthritis by regulating FcγR expression on macrophages

Cited by 51 publications

References 31 publications

Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

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

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

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