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

该提案旨在探索单核细胞/巨噬细胞对垂死/死亡细胞的吞噬作用受损的机制，这可能有助于系统性红斑狼疮的免疫发病机制。我们将研究维生素 D 和 I 型干扰素途径在体外和小鼠狼疮模型体内调节人和小鼠骨髓细胞凋亡细胞摄取和细胞因子分泌中的作用。此外，我们将剖析 I 型干扰素调节体内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，我们将开发治疗策略来恢复垂死细胞的清除，作为纠正小鼠狼疮模型中免疫病理学的一种手段。

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.