Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan; Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan; Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
J Dermatol Sci. 2021 May;102(2):116-125. doi: 10.1016/j.jdermsci.2021.04.004. Epub 2021 Apr 15.
Psoriasis is a chronic inflammatory skin disease. Interleukin (IL)-17A plays a key role in the pathogenesis of psoriasis. Fingolimod, which is available for the treatment of multiple sclerosis, exerts anti-inflammatory effects by sequestrating inflammatory lymphocytes in secondary lymphoid tissues and the thymus. The effect of fingolimod on psoriasis has not been reported yet.
Our objectives were to investigate the effect of fingolimod on psoriasis utilizing mice with imiquimod (IMQ)-induced psoriasiform dermatitis, and explore the possibility of fingolimod as a therapeutic agent for psoriasis.
Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Fingolimod prepared in phosphate-buffered saline (PBS), or PBS alone as a control, was administered intraperitoneally daily from days 0 to 5.
Fingolimod ameliorated IMQ-induced psoriasis dermatitis clinically and histologically. On day 6, the mRNA expression level of IL-17A was lower in the skin of fingolimod-treated mice than in that of PBS-treated mice, whereas it was higher in the inguinal lymph nodes of fingolimod-treated mice than in those of PBS-treated mice. Flow cytometric analyses revealed that fingolimod reduced IL-17A-producing ?d T cells infiltrating into the skin, whereas it increased these cells in the inguinal lymph nodes. Fingolimod inhibited egress of Langerhans cells from the skin to lymph nodes.
Our results demonstrated that fingolimod showed effectiveness for IMQ-induced psoriasiform dermatitis by hindering the emigration of IL-17A-producing ?d T cells from the lymph nodes to the skin, and suggest that fingolimod is a promising candidate for the treatment of psoriasis.
银屑病是一种慢性炎症性皮肤病。白细胞介素（IL）-17A 在银屑病的发病机制中起关键作用。已上市用于治疗多发性硬化症的芬戈莫德通过将炎症性淋巴细胞隔离在次级淋巴组织和胸腺中来发挥抗炎作用。然而，芬戈莫德对银屑病的作用尚未见报道。
我们的目的是利用咪喹莫特（IMQ）诱导的银屑病样皮炎小鼠模型来研究芬戈莫德对银屑病的影响，并探讨芬戈莫德作为银屑病治疗药物的可能性。
在小鼠剃毛背部皮肤上涂抹咪喹莫特，连续 6 天诱导银屑病样皮炎。从第 0 天到第 5 天，每天通过腹腔内注射用磷酸盐缓冲盐水（PBS）配制的芬戈莫德或单独用 PBS 作为对照进行治疗。
芬戈莫德在临床上和组织学上改善了 IMQ 诱导的银屑病样皮炎。在第 6 天，与 PBS 处理的小鼠皮肤相比，芬戈莫德处理的小鼠皮肤中 IL-17A 的 mRNA 表达水平较低，而腹股沟淋巴结中的 IL-17A 表达水平较高。流式细胞术分析显示，芬戈莫德减少了浸润到皮肤中的产生 IL-17A 的?d T 细胞，而增加了腹股沟淋巴结中的这些细胞。芬戈莫德抑制了朗格汉斯细胞从皮肤向淋巴结的迁出。
我们的研究结果表明，芬戈莫德通过阻止产生 IL-17A 的?d T 细胞从淋巴结向皮肤迁移，对 IMQ 诱导的银屑病样皮炎有效，这提示芬戈莫德是治疗银屑病的一种有前途的候选药物。
