The Role of GDF-15 in the Lupus Nephritis

GDF-15 在狼疮性肾炎中的作用

• 批准号: 385829722
• 负责人: Professor Dr. Maciej Lech, Ph.D.
• 金额: --
• 依托单位: Arbeitsgruppe Klinische Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/385829722?language=en
• 关键词: Role; GDF; 15; Lupus; Nephritis

Systemic lupus erythematosus (SLE) leads to an increased extracellular presence of nuclear autoantigens and the activation and proliferation of autoreactive B and T cells and consequently to severe kidney phenotype: lupus nephritis (LN). Our work has shown that RNA- and DNA-containing lupus autoantigens mediate the progression of SLE and lupus nephritis by activation of toll-like receptor-7 and -9, and that this process is mediated by various molecules, e.g. SIGIRR, IRAK-3, PTX3, IRF-4, NLRP3 or ASC. These molecules are responsible for regulation of immune responses in dendritic cells and B cells, which are crucial for the development of the disease. Such molecules that modulate the immune response play an important role in inflammatory diseases.The role of GDF15 in the pathology of SLE and LN is still unknown. We hypothesize that GDF15 deficiency can affect the pathogenesis of SLE for example by increased antigen presentation, cell death and/or other mechanisms which favor a dysregulation of the immune system. Therefore, the aim of this project is to investigate whether 1.) GDF-15 deficient C57BL/6 mice show signs of autoimmunity, 2.) How the SLE and the LN develop in GDF-15-deficient C57BL/6lpr/lpr mice, as well as a clarification of the GDF-15-associated mechanisms which are responsible for the development of the disease 3.) Which functional role has this protein and whether it is suitable for a therapeutic use and 4.) Whether GDF15 is involved in the human LN or whether it can be used as a prognostic marker for the course of the disease.

系统性红斑狼疮 (SLE) 会导致细胞外核自身抗原的增加以及自身反应性 B 和 T 细胞的激活和增殖，从而导致严重的肾脏表型：狼疮性肾炎 (LN)。我们的工作表明，含有 RNA 和 DNA 的狼疮自身抗原通过激活 Toll 样受体 7 和 -9 介导 SLE 和狼疮肾炎的进展，并且该过程是由多种分子介导的，例如SIGIRR、IRAK-3、PTX3、IRF-4、NLRP3 或 ASC。这些分子负责调节树突状细胞和 B 细胞的免疫反应，这对于疾病的发展至关重要。此类调节免疫反应的分子在炎症性疾病中发挥着重要作用。GDF15在SLE和LN病理学中的作用仍不清楚。我们假设 GDF15 缺乏可以影响 SLE 的发病机制，例如通过增加抗原呈递、细胞死亡和/或其他有利于免疫系统失调的机制。因此，该项目的目的是研究 1.) GDF-15 缺陷的 C57BL/6 小鼠是否表现出自身免疫的迹象，2.) SLE 和 LN 在 GDF-15 缺陷的 C57BL/6lpr/lpr 小鼠中如何发展，以及对导致疾病发展的 GDF-15 相关机制的澄清 3.) 该蛋白具有哪些功能作用以及它是否适合治疗用途；4.) GDF15 是否参与人类 LN 或者是否可以用作疾病进程的预后标志物。