Morin Florence, Kavian Niloufar, Nicco Carole, Cerles Olivier, Chéreau Christiane, Batteux Frédéric
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie biologique, Hôpital Cochin, Paris, France.
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
J Invest Dermatol. 2016 Nov;136(11):2158-2167. doi: 10.1016/j.jid.2016.06.624. Epub 2016 Jul 14.
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.
硬皮病样移植物抗宿主病是异基因造血干细胞移植的常见并发症，与系统性硬化症有许多共同特征，如自身抗体产生以及皮肤和内脏器官纤维化。最近有关信号转导和转录激活因子3以及Wnt/β-连环蛋白在纤维化中的作用的报道促使我们使用具有明确安全概况的驱虫药氯硝柳胺，在硬皮病样移植物抗宿主病小鼠模型中研究抑制这两种信号通路的效果。通过B10.D2骨髓和脾细胞移植在BALB/c小鼠中诱导硬皮病样移植物抗宿主病。小鼠每周5天，隔天用氯硝柳胺治疗，共5周。在移植后42天研究临床和生物学特征。氯硝柳胺逆转了包括脱发、血管炎和腹泻在内的临床症状，并预防了皮肤和内脏器官的纤维化。还观察到有益的免疫学效应：氯硝柳胺减少了效应记忆CD4和CD8 T细胞的产生、皮肤和内脏器官的T细胞浸润，并减少了IL-4和IL-13的产生以及自身免疫性B细胞活化。氯硝柳胺在硬皮病样移植物抗宿主病小鼠模型中带来的改善为评估氯硝柳胺在系统性纤维化疾病患者管理中的作用提供了理论依据。
