Cutaneous inflammation is recurrent in systemic lupus erythematosus (SLE), yet mechanisms that drive cutaneous inflammation in SLE are not well defined. Type I IFNs are elevated in nonlesional SLE skin and promote inflammatory responses. Staphylococcus aureus, known to induce IFN production, could play a role in cutaneous inflammation in SLE. We show here that active cutaneous lupus erythematosus lesions are highly colonized (∼50%) by S. aureus. To define the impact of IFNs on S. aureus colonization, we examined the effects of type I and type II IFNs on S. aureus adherence and invasion. An increase in adherent S. aureus was observed after exposure to both IFN-α and -γ, whereas IFN-γ appeared to inhibit invasion of S. aureus. Cutaneous lupus erythematosus lesional skin microarray data and RNA sequencing data from SLE keratinocytes identified repression of barrier gene expression, such as filaggrin and loricrin, and SLE keratinocytes exhibited increased S. aureus-binding integrins. These SLE-associated changes could be replicated by IFN treatment of keratinocytes. Further, SLE keratinocytes exhibited increased binding to S. aureus. Together, these data suggest that chronic exposure to IFNs induces barrier disruption that allows for higher S. aureus colonization in SLE skin.

中文翻译：

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金黄色葡萄球菌定植在狼疮皮肤病变处增加，并由 IFN 介导的屏障破坏促进。

皮肤炎症在系统性红斑狼疮 (SLE) 中反复发作，但在 SLE 中驱动皮肤炎症的机制尚不明确。I 型干扰素在非损伤性 SLE 皮肤中升高并促进炎症反应。已知可诱导 IFN 产生的金黄色葡萄球菌可能在 SLE 的皮肤炎症中起作用。我们在这里表明，活动性皮肤红斑狼疮病变被金黄色葡萄球菌高度定植（~50％）。为了确定干扰素对金黄色葡萄球菌定植的影响，我们检查了 I 型和 II 型干扰素对金黄色葡萄球菌粘附和侵袭的影响。在暴露于 IFN-α 和 -γ 后观察到粘附的金黄色葡萄球菌增加，而 IFN-γ 似乎抑制金黄色葡萄球菌的入侵。来自 SLE 角质形成细胞的皮肤红斑狼疮病变皮肤微阵列数据和 RNA 测序数据确定了屏障基因表达的抑制，例如丝聚蛋白和 loricrin，并且 SLE 角质形成细胞表现出增加的金黄色葡萄球菌结合整合素。这些 SLE 相关的变化可以通过 IFN 处理角质形成细胞来复制。此外，SLE 角质形成细胞表现出与金黄色葡萄球菌的结合增加。总之，这些数据表明长期暴露于 IFN 会导致屏障破坏，从而允许 SLE 皮肤中更高的金黄色葡萄球菌定植。