The pathogenetic role of kerationocytes in cutaneous lupus erythematosus

角质形成细胞在皮肤红斑狼疮发病中的作用

• 批准号: 14516366
• 负责人: Professorin Dr. Miriam Wittmann
• 金额: --
• 依托单位: Hautklinik Mainz
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/14516366?language=en
• 关键词: pathogenetic; role; kerationocytes; cutaneous; lupus

Lupus erythematosus (LE) is an autoimmune disorder and the cutaneous manifestations belong to the most common clinical features of LE. To date there exists no causative treatment regimen. The chronic relapsing course, establishment of irreversible scarring skin defects and hair loss are still unsatisfactory controlled by immunosuppressive therapeutics in a number of patients. Despite extensive investigation, the pathogenesis of lupus-specific cutaneous lesions is unknown. However, a prerequisite for development of effective local therapeutics would be to better understand underlying mechanisms and to identify key factors to target in future therapies. We have learned from different diseases that marked differences of the expression profile and action of immunoregulatory mediators may exist depending on the body compartment affected. Micromilieu settings as well as particular features of resident cells have been shown to be of great importance for the outcome of the immune response. Evidence is accumulating that keratinocytes play a key role in regulating and maintaining the pathology in cutaneous LE. The focus of this study will be on keratinocyte mediators and keratinocyte dependent interactions with lymphocytes present in the surroundings of the epidermal basal layer. Pathophysiological mechanisms involving defective clearance of apoptotic cells, HSP70 and interaction with effector and regulatory T-cells will be examined in detail. It is the aim of this study to clearly define the contribution of resident epidermal cells to the onset and maintenance of cutaneous LE.

红斑狼疮（Lupus erythromatosus， LE）是一种自身免疫性疾病，皮肤表现是狼疮最常见的临床特征。到目前为止还没有任何致病的治疗方案。许多患者的慢性复发过程，不可逆转的瘢痕性皮肤缺损和脱发的建立仍然不满意免疫抑制治疗。尽管广泛的调查，狼疮特异性皮肤病变的发病机制是未知的。然而，开发有效的局部疗法的先决条件是更好地了解潜在的机制，并确定未来治疗的关键因素。我们从不同的疾病中了解到，免疫调节介质的表达谱和作用可能存在显著差异，这取决于受影响的身体隔间。微环境设置以及驻留细胞的特定特征已被证明对免疫反应的结果非常重要。越来越多的证据表明，角质形成细胞在调节和维持皮肤LE病理中起着关键作用。本研究的重点将是角化细胞介质和角化细胞依赖于淋巴细胞存在于表皮基底层周围的相互作用。病理生理机制涉及凋亡细胞的缺陷清除，HSP70和与效应和调节性t细胞的相互作用将被详细检查。本研究的目的是明确常驻表皮细胞在皮肤LE的发生和维持中的作用。