Expanded Double Negative T cells in SLE.

系统性红斑狼疮困扰着100万至200万美国人，并与显著的 发病率和死亡率。虽然更明智地使用免疫抑制药物并及时治疗 并发症改善了整体生存和生活质量，我们仍然缺乏特效药物， 充分了解相关的致病过程和有价值的疾病生物标志物。在……里面 此外，我们对地方、特定器官机制的理解涉及执行 组织损伤是有限的。扩大的T细胞群缺失了CD_4和CD_8 系统性红斑狼疮患者外周血表面双阴性T细胞 红斑狼疮，帮助自体B细胞产生免疫球蛋白和dsDNA抗体， 产生促炎性白介素17，并侵入组织引起炎症。这 应用建议使用最先进的新技术，包括光谱细胞术， 单细胞RNA测序和一系列新型工程小鼠研究细胞的多样性 狼疮易感小鼠外周血和肾脏中的双阴性T细胞群 系统性红斑狼疮患者并了解炎性环境 为他们这一代人做出了贡献。同时，还提出了一些实验，以了解 炎症细胞因子作用于肾脏驻留细胞，使炎症得以建立。 拟议中的实验将为开发抑制 病原性双阴性T细胞的产生和组织的建立 发炎。

Systemic lupus erythematosus afflicts 1 to 2 million Americans and is associated with significant morbidity and mortality. While wiser use of immunosuppressive drugs and prompt treatment of complications have improved the overall survival and quality of life, we still lack specific drugs, full understanding of the involved pathogenic processes and valuable disease biomarkers. In addition, our understanding of local, organ-specific mechanisms involved in the execution of tissue injury is limited. An expanded population of T cells missing CD4 and CD8 from the surface (double negative T cells) in the peripheral blood of patients with systemic lupus erythematosus, helps autologous B cells to produce immunoglobulin and dsDNA antibodies, produces the proinflammatory interleukin 17 and invades tissues to cause inflammation. This application proposes the use of state-of-the-art new technologies including spectral cytometry, single cell RNA sequencing and series of novel engineered mice to study the diversity of the double negative T cell population in the peripheral blood and kidneys of lupus-prone mice and people with systemic lupus erythematosus and understand how an inflammatory environment contributes to their generation. In parallel, experiments are proposed to understand how inflammatory cytokines act on kidney resident cells to enable the establishment of inflammation. The proposed experiments will inform the development of approaches to suppress the generation of pathogenic double negative T cells and prevent the establishment of tissue inflammation.