Exploring differences in NETosis in systemic lupus erythematosus (SLE)

系统性红斑狼疮（SLE）是一种主要影响女性的自身免疫性疾病。重要的是，这种疾病的临床特征是高度异质性的，这为个性化治疗提供了潜力。最近已经确定，中性粒细胞可以挤出其内容物通过中性粒细胞胞外陷阱（NET）。这些都是有效的免疫系统刺激物，可能驱动SLE的炎症过程。此外，NETs何时和如何形成的差异可能解释SLE的一些临床和免疫学差异。本项目将探索SLE患者神经网络功能的新方面。通过与工业合作伙伴的合作，我们将使用高通量荧光显微镜来研究NET的形成和去除。NET含量的变化及其对下游免疫活性的影响将被确定。最后，高通量分析的发展将使我们能够筛选药物文库，以寻找新的NET形成和功能调节剂。我们的目标是确定SLE的新治疗方法以及个性化治疗的稳健方法。

Systemic lupus erythematosus (SLE) is an autoimmune disorder predominantly affecting women. Importantly the clinical features of this disease are highly heterogeneous which offers the potential for personalised therapies.Recently it has been identified that neutrophils can extrude their contents through as a neutrophil extracellular trap (NET). These are potent immune system stimulators and may drive the inflammatory process in SLE. Furthermore, difference between when and how NETs form may explain some of the clinical and immunological variation in SLE. This project will explore novel aspects of NET function in patients with SLE. In collaboration with the industrial partner wewill use high throughput fluorescent microscopy to study both NET formation and removal. Variation in NET content and the consequences for downstream immune activity will be identified. Finally the development of high throughput assayswill allow us to screen drug libraries for novel modulators of NET formation and function. We aim to identify novel treatments for SLE along with a robust approach for personalisation of treatment.