Galectin-3 Is Critical for the Development of the Allergic Inflammatory Response in a Mouse Model of Atopic Dermatitis

Saegusa, Jun; Hsu, Daniel K.; Chen, Huan Yuan; Yu, Liang; Fermin, Agnes; Fung, Maxwell A.; Liu, Fu‐Tong

doi:10.2353/ajpath.2009.080500

Cited by 81 publications

(87 citation statements)

References 38 publications

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“…Knockout mice displayed abrogated Th2, but enhanced Th1 responses as indicated by low IL-4 and high IFN-γ and IL-12 expression. 93 Similar results were found in an OVA-induced asthma model, where infiltration of eosinophils, macrophages, and neutrophils was significantly lower in BAL of galectin-3 knockout mice. Additionally, the concentrations of IgE, IL-4, and IFN-γ in BAL were lower in galectin-3 knockout mice, indicative of attenuated Th2 responses.…”

Section: Galectin-3 In the Pathogenesis Of Allergic Diseasessupporting

confidence: 75%

Galectin-3 and Inflammation

Wan

Liu

2016

Glycobiology Insights

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ABSTRACT:Galectins are a family of β-galactoside-binding proteins that share a consensus sequence in the carbohydrate recognition domain (CRD). Galectin-3 is the most widely studied family member and can be found in the cellular cytoplasm and nucleus, as well as extracellularly in various tissues. The 30-kDa molecule contains an N-terminal proline-rich domain that is important for its oligomerization and a C-terminal CRD for carbohydrate-binding activity. Many studies have shown that galectin-3 may regulate inflammation through a variety of mechanisms. Endogenous galectin-3 has been shown to be involved in the pathogenesis of various diseases, such as fibrosis in the lung, liver, and heart, diabetes mellitus, coronary artery disease, and allergic diseases. In this review, we briefly discuss the pro-or anti-inflammatory roles, as well as potential clinical implications of galectin-3 in these disorders.

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Section: Galectin-3 In the Pathogenesis Of Allergic Diseasessupporting

confidence: 75%

Galectin-3 and Inflammation

Wan

Liu

2016

Glycobiology Insights

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“…Lack of galectin-3 induces a higher Th1-polarized response in atopic dermatitis models, infections with Schistosoma monsoni, Toxoplasma gondii, and as a part of tumor immunity (59,92,94,95). In addition, lack of galectin-3 also restrains IL-4-induced alternative macrophage (M2) activation (93).…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Facilitates Neutrophil Recruitment as an Innate Immune Response to a Parasitic Protozoa Cutaneous Infection

Bhaumik

St-Pierre

Milot

et al. 2013

The Journal of Immunology

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When infection occurs, neutrophils rapidly migrate to the affected site. Although the neutrophils neutralize microorganisms, they can also cause tissue damage or render invasion pathways to pathogens. Thus, the migration could be either beneficial or unfavorable in the initial control of infection. Studies on neutrophil recruitment revealed its complexity, especially in terms of the regulation of its initiation. Galectin-3 is a member of the galectin family that has an affinity for β-galactoside containing glycoconjugates. In this study, we investigated the role of galectin-3 in neutrophil migration and the biological significance of the rapid migration of neutrophils in an experimental parasitic cutaneous infection with Leishmania major. When the substrain of L. major, LV39, was infected, lack of galectin-3 impaired neutrophil recruitment in the footpads and the draining lymph nodes 1 d following infection. Reduced number of recruited neutrophils correlated with local high parasite burdens. In contrast, neutrophil migration, induced by the other L. major substrain, Friedlin, was unaffected, and the initial parasite burden remained similar in galectin-3 null mice as compared with wild-type mice. Infection with L. major LV39 but not Friedlin induced higher levels of extracellular release of galectin-3. Further, galectin-3 alone was able to initiate neutrophil migration even though galectin-3 is not a chemoattractant for neutrophils. Thus, our data suggest that once extracellularly released, galectin-3 can act as a damage-associated molecular pattern to facilitate early neutrophil migration, which is beneficial in the initial control of the Leishmania infection.

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“…Through direct inhibition of IL-12 production in DCs and macrophages, gal3 suppresses Th1 immune responses and exacerbates Toxoplasma gondii and Rhodococcus equi infections in mice (6,7). Also by inhibiting IL-12 production, gal3 promotes the Th2 response in mouse models of atopic dermatitis and asthma (8,9). In contrast, gal3 suppresses the Th2 response in infection by Paracoccidioides brasiliensis (10).…”

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confidence: 99%

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

Liu

et al. 2013

The Journal of Immunology

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Galectin-3 (gal3) is known for its immunoregulatory functions in infectious, autoimmune, and inflammatory diseases. However, little is known about its regulatory role in the host's IL-17A response to infection. Using a mouse model of histoplasmosis in which both Th1 and Th17 responses contribute to fungal clearance, we investigated how gal3 regulates IL-17A responses. Our study showed that Histoplasma infection induced gal3−/− dendritic cells to produce significantly higher levels of IL-23, TGF-β1, and IL-1β than did gal3+/+ cells. Infected by the same inoculum of Histoplasma, gal3−/− mice had lower fungal burden and produced higher levels of IL-23/IL-17–axis cytokines and lower levels of IL-12 and IFN-γ. Additionally, there was an increase in Th17 cells and a reduction in Th1 cells in infected gal3−/− mice. In vitro Th1/Th17-skewing experiments excluded the intrinsic effect of gal3 on Th cell differentiation. Although neutrophils from both gal3+/+ and gal3−/− mice produced IL-17A upon IL-23 stimulation, their contribution to IL-17A production was greater in gal3−/− mice than in gal3+/+ mice. Compared with gal3+/+ dendritic cells, adoptive transfer of gal3−/− dendritic cells resulted in production of significantly higher levels of IL-17–axis cytokines and reduced fungal burden. It appears that reduced fungal burden and preferential IL-17A response in gal3−/− mice by both Th17 cells and neutrophils were the result of preferential production of IL-23/IL-17–axis cytokines by dendritic cells. Our study showed that gal3 negatively regulates IL-17A responses through inhibition of IL-23/IL-17–axis cytokine production by dendritic cells.

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Galectin-3 Is Critical for the Development of the Allergic Inflammatory Response in a Mouse Model of Atopic Dermatitis

Cited by 81 publications

References 38 publications

Galectin-3 and Inflammation

Galectin-3 and Inflammation

Galectin-3 Facilitates Neutrophil Recruitment as an Innate Immune Response to a Parasitic Protozoa Cutaneous Infection

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

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