Abstract
Tim-3 is a cell surface molecule preferentially expressed in Th1 and Th17 cells. Galectin-9 is a ligand for Tim-3 and the binding of galectin-9 to Tim-3 induces apoptosis. We recently developed a stable form of galectin-9 (sGal-9) by partial deletion of the linker peptide. In this study, we characterized the therapeutic effects of sGal-9 on inflammatory reactions in contact hypersensitivity and IL-23-induced psoriatic mouse models. In contact hypersensitivity in mice, the ear swelling response was suppressed by sGal-9. In vitro treatment with sGal-9 resulted in cell apoptosis of CD4, CD8, and hepatic NK cells. sGal-9-treated mice had decreased IFN-gamma- and IL-17-producing T cells. Similarly, sGal-9 reduced epidermal thickness and dermal cellular infiltrate levels in IL-23-induced psoriasis-like skin inflammation. This was accompanied by decreased skin lesion levels of IL-17 and IL-22. sGal-9 may be a unique and useful therapeutic tool for the treatment of Th1- and/or Th17-mediated skin inflammation.
MeSH terms
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Animals
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Apoptosis / drug effects
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Cell Proliferation / drug effects
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Chemokines / metabolism
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Croton Oil / toxicity
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Cytokines / metabolism
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Dermatitis, Contact / etiology
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Dermatitis, Contact / prevention & control*
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Dermatitis, Irritant / etiology
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Dermatitis, Irritant / immunology
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Dermatitis, Irritant / prevention & control
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Dinitrofluorobenzene / toxicity
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Galectins / administration & dosage
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Galectins / metabolism
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Galectins / pharmacology*
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Hepatitis A Virus Cellular Receptor 2
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Interleukin-17 / metabolism
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Interleukin-23
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Killer Cells, Natural / cytology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / metabolism
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Ligands
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Lymph Nodes / cytology
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Lymph Nodes / drug effects
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Lymph Nodes / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Psoriasis / chemically induced
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Psoriasis / prevention & control*
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Receptors, Virus / metabolism
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Skin / drug effects*
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Skin / immunology
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Skin / metabolism
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism
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Th1 Cells / immunology
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Th1 Cells / metabolism
Substances
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Chemokines
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Cytokines
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Galectins
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Havcr2 protein, mouse
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Hepatitis A Virus Cellular Receptor 2
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Interleukin-17
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Interleukin-23
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Ligands
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Receptors, Virus
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galectin 9, mouse
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Croton Oil
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Dinitrofluorobenzene