Dyring-Andersen B, Bonefeld C M, Bzorek M, Løvendorf M B, Lauritsen J P H, Skov L, Geisler C
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Scand J Immunol. 2015 Jul;82(1):84-91. doi: 10.1111/sji.12304.
The vitamin D analogue calcipotriol is an immunomodulatory drug widely used to treat psoriasis; however, how calcipotriol affects the immune cells in psoriasis lesions is not fully understood. The aim of this study was to investigate the effect of calcipotriol on the frequency of CD4(+) and CD8(+) T cells and innate lymphoid cells (ILC) and their production of IL-17A, IFN-γ and IL-22 in psoriasis lesions in patients with chronic plaque psoriasis. Eighteen patients with psoriasis were included, and two similar psoriasis lesions were chosen for each patient. One lesion was treated with calcipotriol (50 μg/g) and the other with vehicle twice a day for 14 days. The clinical effect was measured by degree of erythema, scaling and induration in each lesion (SUM score). Skin biopsies were collected for histological and immunohistochemical analyses. Skin-derived cells were isolated and analysed by flow cytometry. After 14 days of treatment with calcipotriol, a significant clinical and histological effect was seen; however, we found no differences in the frequency of CD4(+) and CD8(+) T cells or ILC between calcipotriol- and vehicle-treated skin. The main finding was a significant decrease in CD8(+) IL-17(+) T cells in skin-derived cells from calcipotriol-treated skin, which was further supported by the absence of CD8(+) IL-17(+) T cells in immunohistochemical staining of calcipotriol-treated skin. No changes in the frequency of IL-22(+) or IFN-γ(+) cells were observed. Our findings show that the vitamin D analogue calcipotriol reduces the frequency of CD8(+) IL-17(+) T cells in psoriasis lesions concomitant with clinical improvement.
维生素D类似物卡泊三醇是一种广泛用于治疗银屑病的免疫调节药物;然而,卡泊三醇如何影响银屑病皮损中的免疫细胞尚未完全明确。本研究旨在探讨卡泊三醇对慢性斑块状银屑病患者银屑病皮损中CD4(+)和CD8(+) T细胞及固有淋巴细胞(ILC)频率及其IL-17A、IFN-γ和IL-22产生的影响。纳入18例银屑病患者,为每位患者选择两个相似的银屑病皮损。一个皮损用卡泊三醇(50 μg/g)治疗,另一个用赋形剂治疗,每天两次,共14天。通过每个皮损的红斑、鳞屑和硬结程度(SUM评分)来衡量临床效果。采集皮肤活检标本进行组织学和免疫组织化学分析。分离皮肤来源的细胞并通过流式细胞术进行分析。卡泊三醇治疗14天后,观察到显著的临床和组织学效果;然而,我们发现卡泊三醇治疗组和赋形剂治疗组皮肤之间的CD4(+)和CD8(+) T细胞或ILC频率没有差异。主要发现是卡泊三醇治疗组皮肤来源细胞中CD8(+) IL-17(+) T细胞显著减少,卡泊三醇治疗皮肤的免疫组织化学染色中缺乏CD8(+) IL-17(+) T细胞进一步支持了这一发现。未观察到IL-22(+)或IFN-γ(+)细胞频率的变化。我们的研究结果表明,维生素D类似物卡泊三醇在改善临床症状的同时降低了银屑病皮损中CD8(+) IL-17(+) T细胞的频率。