Impact of immunoglobulin G and Fc-gamma-receptors on osteoblast and osteoclast development and function in vitro and in vivo

免疫球蛋白 G 和 Fc-γ 受体对体外和体内成骨细胞和破骨细胞发育和功能的影响

• 批准号: 168880268
• 负责人: Professor Dr. Falk Nimmerjahn
• 金额: --
• 依托单位: Lehrstuhl für Genetik - AG Falk Nimmerjahn
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/168880268?language=en
• 关键词: Impact; immunoglobulin; Fc; gamma; receptors

Autoimmune diseases are a major cause for reduced life expectancy and quality of life in the developed countries. Immunoglobulin G (IgG) antibodies play a major role in tissue inflammation and destruction during autoimmune diseases such as rheumatoid arthritis. IgG antibodies recognising healthy tissues (autoantibodies) efficiently, recruit innate immune effector cells including neutrophils and macrophages resulting in inflammation of the target tissue such as the joints. In addition, cartilage destruction and large areas of bone erosion can be identified, resulting in functional impairment of the joints. Bone homeostasis is regulated by balanced bone resorption mediated by osteoclasts and bone generation by osteoblasts. During rheumatoid arthritis this balance is impaired and osteoclasts dependent bone destruction predominates. This project will study the crosstalk between autoantibodies causing tissue inflammation and osteoclasts responsible for bone destruction. We will analyse the expression pattern of cell surface receptors necessary for recognition of IgG antibodies (so called Fcy-receptors) during osteoclast maturation and the impact of activation of these receptors on osteoclast development, activation and the resulting changes in bone homeostasis in vitro and in vivo.

自身免疫性疾病是发达国家预期寿命和生活质量降低的主要原因。免疫球蛋白 G (IgG) 抗体在类风湿性关节炎等自身免疫性疾病期间的组织炎症和破坏中发挥着重要作用。 IgG 抗体可有效识别健康组织（自身抗体），招募先天免疫效应细胞，包括中性粒细胞和巨噬细胞，导致关节等靶组织发炎。此外，还可以发现软骨破坏和大面积骨侵蚀，导致关节功能受损。骨稳态通过破骨细胞介导的平衡骨吸收和成骨细胞介导的骨生成来调节。在类风湿性关节炎期间，这种平衡受到损害，破骨细胞依赖性骨质破坏占主导地位。该项目将研究引起组织炎症的自身抗体与负责骨质破坏的破骨细胞之间的串扰。我们将分析破骨细胞成熟过程中识别 IgG 抗体（所谓的 Fcy 受体）所需的细胞表面受体的表达模式，以及这些受体的激活对破骨细胞发育、激活以及由此产生的体外和体内骨稳态变化的影响。