Raposo R A, Gupta R, Abdel-Mohsen M, Dimon M, Debbaneh M, Jiang W, York V A, Leadabrand K S, Brown G, Malakouti M, Arron S, Kuebler P J, Wu J J, Pillai S K, Nixon D F, Liao W
Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
J Eur Acad Dermatol Venereol. 2015 Oct;29(10):1951-7. doi: 10.1111/jdv.13091. Epub 2015 Mar 23.
Psoriasis patients have relatively infrequent cutaneous viral infections compared to atopic dermatitis patients. Increased expression of four antiviral proteins (MX1, BST2, ISG15 and OAS2) has been reported in psoriatic skin and genetic studies of psoriasis have identified susceptibility genes in antiviral pathways.
To determine if psoriasis is associated with pervasive expression of antiviral genes in skin and blood.
We performed RNA sequencing on skin samples of 18 subjects with chronic plaque psoriasis and 16 healthy controls. We examined the expression of a predefined set of 42 antiviral genes, each of which has been shown in previous studies to inhibit viral replication. In parallel, we examined antiviral gene expression in atopic dermatitis, non-lesional psoriatic skin and psoriatic blood. We performed HIV-1 infectivity assays in CD4+ peripheral blood T cells from psoriatic and healthy individuals.
We observed significant overexpression of 16 antiviral genes in lesional psoriatic skin, with a greater than two-fold increase in ISG15, RSAD2, IRF7, MX2 and TRIM22 (P < 1E-07). None of these genes was overexpressed in atopic dermatitis skin (P < 0.0001) or non-lesional psoriatic skin. In contrast to the skin compartment, no differences in antiviral gene expression were detected in the peripheral blood of psoriasis cases compared to healthy controls. CD4+ T cells from both psoriatic and healthy patients supported HIV-1 infection at a similar rate.
Our findings highlight psoriasis as an inflammatory disease with cutaneous but not systemic immune activation against viral pathogens.
与特应性皮炎患者相比,银屑病患者皮肤病毒感染相对较少。据报道,银屑病皮肤中四种抗病毒蛋白(MX1、BST2、ISG15和OAS2)表达增加,银屑病的遗传学研究已确定抗病毒途径中的易感基因。
确定银屑病是否与皮肤和血液中抗病毒基因的普遍表达有关。
我们对18例慢性斑块状银屑病患者和16例健康对照者的皮肤样本进行了RNA测序。我们检测了一组预先定义的42种抗病毒基因的表达,先前的研究已表明每种基因均可抑制病毒复制。同时,我们检测了特应性皮炎、非皮损性银屑病皮肤和银屑病血液中的抗病毒基因表达。我们对银屑病患者和健康个体的CD4 + 外周血T细胞进行了HIV-1感染性测定。
我们观察到皮损性银屑病皮肤中有16种抗病毒基因显著过表达,ISG15、RSAD2、IRF7、MX2和TRIM22的表达增加了两倍以上(P < 1E-07)。这些基因在特应性皮炎皮肤(P < 0.0001)或非皮损性银屑病皮肤中均未过表达。与皮肤部位不同,银屑病患者外周血中抗病毒基因表达与健康对照相比未检测到差异。银屑病患者和健康患者的CD4 + T细胞支持HIV-1感染的速率相似。
我们的研究结果突出表明银屑病是一种炎症性疾病,具有针对病毒病原体的皮肤而非全身免疫激活。