title: Improvement of Sclerodermatous Graft-Versus-Host Disease in Mice by Niclosamide.
abstract: Sclerodermatous graft-versus-host disease, a frequent complication of allogeneic hematopoietic stem cell graft, shares many features with systemic sclerosis, such as production of autoantibodies and fibrosis of skin and inner organs. Recent reports on the implication of signal transducer and activator of transcription 3 and of Wnt/β-catenin in fibrosis have prompted us to investigate the effects of the inhibition of both signaling pathways in a mouse model of sclerodermatous graft-versus-host disease, using niclosamide, an anthelmintic drug, with a well-defined safety profile. Sclerodermatous graft-versus-host disease was induced in BALB/c mice by B10.D2 bone marrow and spleen cell transplantation. Mice were treated every other day, 5 days a week, for 5 weeks by niclosamide. Clinical and biological features were studied 42 days after transplantation. Niclosamide reversed clinical symptoms including alopecia, vasculitis, and diarrhea and prevented fibrosis of the skin and visceral organs. Beneficial immunological effects were also observed: niclosamide decreased the production of effector memory CD4 and CD8 T cells, T-cell infiltration of the skin and visceral organs, and decreased productions of IL-4 and IL-13, and autoimmune B-cell activation. The improvement provided by niclosamide in the mouse model of sclerodermatous graft-versus-host disease provides a rationale for the evaluation of niclosamide in the management of patients affected by systemic fibrotic disease.
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie biologique, Hôpital Cochin, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Morin
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie biologique, Hôpital Cochin, Paris, France.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Kavian
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Nicco
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cerles
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Chéreau
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie biologique, Hôpital Cochin, Paris, France. Electronic address: frederic.batteux@aphp.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D009534:Niclosamide / Q000627:therapeutic use*; D012594:Scleroderma, Localized / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D009534:Niclosamide