Aberrant macrophages, central to discoid lupus erythematosus?

异常巨噬细胞是盘状红斑狼疮的核心？

• 批准号: 233414269
• 负责人: Dr. Jea-Hyun Baek
• 金额: --
• 依托单位: Harvard Institutes of Medicine (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/233414269?language=en
• 关键词: Aberrant; macrophages; central; discoid; lupus

Discoid lupus erythematosus (DLE) is a specific form of a chronic inflammatory autoimmune disorder that occurs in skin. DLE is common in patients with lupus and is often the first manifestation. Through unknown mechanisms, the onset of DLE as well as some SLE cases is found in a prominent population of genetically predisposed individuals, which is closely related with exposure to sunlight (ultraviolet light; UV). Recently, it has been shown in lupus-susceptible mouse models that Colony Stimulating Factor-1 (CSF-1) can have a significant role in the pathogenesis of SLE and to incite cutaneous lupus symptoms recruiting reactive macrophages to the inflamed skin after exposure to UV. CSF-1 is an important cytokine for monocyte and macrophage development and is expressed in skin by keratinocytes in epidermis and fibroblasts in dermis. Interestingly, in lupus-susceptible mouse models, macrophages have been found to destroy CSF-1 expressing skin-resident cells. Based upon these findings, we hypothesize that aberrant macrophages drive UVB-incited DLE in lupus-susceptible mouse models.Our aim in this study is first to examine the role of aberrant macrophages in the pathogenesis of DLE. Furthermore, we want to dissect innate immune mechanism triggering autoimmune reactions and tissue regeneration in the skin, employing different transgenic mouse models being present, partially established in the host institute, which will allow us to decipher the mechanisms leading to DLE, SLE and other autoimmune diseases and to engineer new human translational components, such as biomarkers and therapeutic targets, for lupus patients.

盘状红斑狼疮（DLE）是一种发生在皮肤中的慢性炎症性自身免疫性疾病的特殊形式。DLE在狼疮患者中很常见，通常是首发症状。通过未知的机制，DLE以及一些SLE病例的发病在遗传易感个体的突出人群中发现，这与暴露于阳光（紫外线; UV）密切相关。最近，在狼疮易感小鼠模型中已经显示，集落刺激因子-1（CSF-1）在SLE的发病机制中具有重要作用，并且在暴露于UV后激发皮肤狼疮症状，将反应性巨噬细胞募集到发炎的皮肤。CSF-1是单核细胞和巨噬细胞发育的重要细胞因子，并且在皮肤中由表皮中的角质形成细胞和真皮中的成纤维细胞表达。有趣的是，在狼疮易感小鼠模型中，已发现巨噬细胞破坏表达CSF-1的皮肤驻留细胞。基于这些发现，我们假设异常巨噬细胞驱动UVB诱导的DLE在狼疮易感小鼠models. We的目的是在这项研究中首先检查异常巨噬细胞在DLE的发病机制中的作用。此外，我们希望解剖引发自身免疫反应和皮肤组织再生的先天免疫机制，采用目前存在的不同转基因小鼠模型，部分建立在宿主研究所，这将使我们能够破译导致DLE，SLE和其他自身免疫性疾病的机制，并为狼疮患者设计新的人类翻译组件，如生物标志物和治疗靶点。