title: Stable form of galectin-9, a Tim-3 ligand, inhibits contact hypersensitivity and psoriatic reactions: a potent therapeutic tool for Th1- and/or Th17-mediated skin inflammation.
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.
authors.affiliation: Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Niwa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Satoh
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hosoya
authors.forename: Kazumi
authors.initials: K
authors.lastname: Saeki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yokozeki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003436:Croton Oil / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology / Q000517:prevention & control*; D017453:Dermatitis, Irritant / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D037161:Galectins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000139:chemically induced / Q000517:prevention & control*; D011991:Receptors, Virus / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D020381:Interleukin-17; D053759:Interleukin-23; D008024:Ligands; D011991:Receptors, Virus; C508186:galectin 9, mouse; D003436:Croton Oil; D004139:Dinitrofluorobenzene