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具有高度的异质性，这为个性化治疗提供了可能性。最近发现，中性粒细胞可以通过中性粒细胞外陷阱(Net)的形式将其内容物排出体外。这些都是强大的免疫系统刺激剂，可能会推动SLE的炎症过程。此外，Net形成的时间和方式之间的差异可能解释了SLE的一些临床和免疫学变化。该项目将探索SLE患者网络功能的新方面。在与工业伙伴的合作中，我们将使用高通量荧光显微镜来研究网络的形成和去除。将确定净含量的变化以及对下游免疫活动的影响。最后，高通量分析的发展将使我们能够筛选药物文库，寻找新的网络形成和功能调节器。我们的目标是确定治疗系统性红斑狼疮的新方法，以及个性化治疗的强大方法。

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.