Type I interferon: potential therapeutic target for psoriasis?
Type I interferon: potential therapeutic target for psoriasis?
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I型干扰素：牛皮癣的潜在治疗靶标？
DOI：
10.1371/journal.pone.0002737
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发表时间：
2008-07-16
期刊：
影响因子：
3.7
通讯作者：
Jallal, Bahija
中科院分区：
文献类型：
--
作者：
Yao, Yihong;Richman, Laura;Morehouse, Chris;de los Reyes, Melissa;Higgs, Brandon W.;Boutrin, Anmarie;White, Barbara;Coyle, Anthony;Krueger, James;Kiener, Peter A.;Jallal, Bahija
银屑病是一种免疫介导的疾病，其特征在于异常的表皮分化、表面鳞屑形成和显著的皮肤炎症。为了更好地了解这种疾病的发病机制和确定潜在的介质，我们使用全基因组阵列分析配对的皮损和非皮损银屑病皮肤和健康供体的皮肤。我们观察到I型干扰素（IFN）诱导的基因和基因组特征，表明T细胞和树突状细胞浸润在皮损的皮肤稳健的过度表达。与非病变皮肤相比，在病变皮肤中观察到IFN-α亚型的mRNA上调。在大多数病变皮肤活检中观察到成熟树突状细胞和2种I型IFN诱导蛋白STAT 1和ISG 15的富集。IFN-γ和TNF-α诱导基因标记的一致性过表达发生在相同的疾病部位。皮损皮肤中TNF-α的上调和TNF-α诱导基因特征的升高强调了这种细胞因子在银屑病中的重要性;这些数据描述了抗TNF-α药物治疗活性的分子基础。此外，这些发现暗示I型干扰素在银屑病的发病机制。I型干扰素及其相关基因在银屑病皮肤中的一致和显著上调表明I型干扰素可能是银屑病治疗中的潜在治疗靶点。
Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors. We observed robust overexpression of type I interferon (IFN)–inducible genes and genomic signatures that indicate T cell and dendritic cell infiltration in lesional skin. Up-regulation of mRNAs for IFN-α subtypes was observed in lesional skin compared with nonlesional skin. Enrichment of mature dendritic cells and 2 type I IFN–inducible proteins, STAT1 and ISG15, were observed in the majority of lesional skin biopsies. Concordant overexpression of IFN-γ and TNF-α–inducible gene signatures occurred at the same disease sites. Up-regulation of TNF-α and elevation of the TNF-α–inducible gene signature in lesional skin underscore the importance of this cytokine in psoriasis; these data describe a molecular basis for the therapeutic activity of anti–TNF-α agents. Furthermore, these findings implicate type I IFNs in the pathogenesis of psoriasis. Consistent and significant up-regulation of type I IFNs and their associated gene signatures in psoriatic skin suggest that type I IFNs may be potential therapeutic targets in psoriasis treatment.
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