Impaired phagocyte function in the immunopathogenesis of systemic lupus erythematosus (SLE): Etiology and therapeutic intervention (P12)

系统性红斑狼疮 (SLE) 免疫发病机制中吞噬细胞功能受损：病因学和治疗干预 (P12)

• 批准号: 275544974
• 金额: --
• 依托单位: Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie (einschließlich Arbeitsbereich Physikalische Medizin)
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/275544974?language=en
• 关键词: Impaired; phagocyte; function; immunopathogenesis; systemic

This proposal aims at exploring the mechanisms causing impaired phagocytosis of dying/dead cells by monocytes/macrophages, which may contribute to the immunopathogenesis of SLE. We will investigate the role of vitamin D and type I interferon pathways in regulating apoptotic cell uptake and cytokine secretion by human and mouse myeloid cells in vitro and in murine lupus models in vivo. Further, we will dissect the mechanisms by which type I interferons modulate the development, apoptotic cell clearing capacity and the downstream immune responses of phagocytic subsets in vivo. Finally, we will develop therapeutic strategies to restore clearance of dying cells as a means to correct immunopathology in murine lupus models.

本研究旨在探讨单核/巨噬细胞对死亡/死亡细胞吞噬功能受损的机制，这可能与SLE的免疫发病机制有关。我们将在体外和体内研究维生素D和I型干扰素通路在调节人和小鼠髓系细胞的凋亡细胞摄取和细胞因子分泌方面的作用。此外，我们将剖析I型干扰素在体内调节吞噬细胞亚群的发育、凋亡细胞清除能力和下游免疫反应的机制。最后，我们将制定治疗策略，以恢复死亡细胞的清除，作为纠正小鼠狼疮模型免疫病理学的一种手段。