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

本研究旨在探讨单核/巨噬细胞吞噬死亡细胞功能受损的机制，这可能有助于SLE的免疫发病机制。我们将研究维生素D和I型干扰素途径在调节凋亡细胞摄取和细胞因子分泌的人类和小鼠骨髓细胞在体外和在小鼠狼疮模型在体内的作用。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，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。

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.