KFO 249: Defects of the Innate Immune System in Autoinflammation and Autoimmunity

先天免疫系统在防御微生物和处理炎症过程中起着核心作用。临床研究单位侧重于确定由先天免疫系统缺陷引起的遗传性疾病的新病理生理机制。这些疾病的表型谱分析包括周期性发热、红斑狼疮的皮肤和全身变异，以及aicardii - gouti<e:1>综合征（一种与自身免疫相关的脑病）。这些疾病的一个共同特征是，它们潜在的遗传变化指向迄今为止未知的与先天免疫系统有关的机制。在遗传决定的自身炎症和自身免疫紊乱的基础上，先天免疫系统基因突变的影响将由临床研究单位的八个小组在分子和细胞水平以及动物模型和患者中进行分析。此外，科学家们将把基因突变的影响与临床数据联系起来。预期的结果应该为先天免疫系统中发生的缺陷的分子发病机制提供基本的见解。此外，研究结果应支持临床治疗的发展。在这方面，基因产物、它们的相互作用伙伴和所涉及的信号传导途径不仅代表了改进诊断可能性的基础。此外，它们是潜在的靶分子，可以从根本上促进新的因果导向治疗方法的发展。

The innate immune system plays a central role in defending microorganisms and in dealing with inflammatory processes. The Clinical Research Unit focusses on identifying new pathophysiological mechanisms of hereditary diseases caused by defects in the innate immune system. The phenotypic spectrum of the disorders analysed includes periodic fever, cutane and systemic variants of lupus erythematosus as well as the Aicardi-Goutières syndrome, an autoimmunity-related encephalopathy. A common characteristic of these diseases is the fact that their underlying genetic changes point to so far unknown mechanisms in relation to the innate immune system. On the basis of genetically determined autoinflammatory and autoimmunological disorders, the effects of mutations in genes of the innate immune system will be analysed by eight subgroups of the Clinical Research Unit at the molecular and cellular level as well as in animal models and in patients. Furthermore, the scientists will correlate effects of genetic mutations with clinical data. The expected results are supposed to provide fundamental insights into the molecular pathogenesis of defects occurring in the innate immune system. In addition, the findings shall support the development of clinical therapies. In this regard, the gene products, their interaction partners and the signalling pathways involved do not only represent the basis for improved diagnostic possibilities. Moreover, they are potential target molecules, which can essentially contribute to the development of new causally oriented therapy approaches.