Department of Medicine, Beth Israel Deaconess Medical Center, Harvard, Medical School, Boston, Massachusetts, USA.
Curr Opin Rheumatol. 2023 Mar 1;35(2):107-116. doi: 10.1097/BOR.0000000000000887. Epub 2022 Jul 5.
Lupus nephritis is associated with significant mortality and morbidity. We lack effective therapeutics and biomarkers mostly because of our limited understanding of its complex pathogenesis. We aim to present an overview of the recent advances in the field to gain a deeper understanding of the underlying cellular and molecular mechanisms involved in lupus nephritis pathogenesis.
Recent studies have identified distinct roles for each resident kidney cell in the pathogenesis of lupus nephritis. Podocytes share many elements of innate and adaptive immune cells and they can present antigens and participate in the formation of crescents in coordination with parietal epithelial cells. Mesangial cells produce pro-inflammatory cytokines and secrete extracellular matrix contributing to glomerular fibrosis. Tubular epithelial cells modulate the milieu of the interstitium to promote T cell infiltration and formation of tertiary lymphoid organs. Modulation of specific genes in kidney resident cells can ward off the effectors of the autoimmune response including autoantibodies, cytokines and immune cells.
The development of lupus nephritis is multifactorial involving genetic susceptibility, environmental triggers and systemic inflammation. However, the role of resident kidney cells in the development of lupus nephritis is becoming more defined and distinct. More recent studies point to the restoration of kidney resident cell function using cell targeted approaches to prevent and treat lupus nephritis.
狼疮肾炎与较高的病死率和发病率相关。我们缺乏有效的治疗方法和生物标志物，主要是因为我们对其复杂发病机制的了解有限。我们旨在概述该领域的最新进展，以更深入地了解狼疮肾炎发病机制中涉及的细胞和分子机制。
最近的研究确定了固有肾细胞在狼疮肾炎发病机制中的独特作用。足细胞具有先天和适应性免疫细胞的许多特征，它们可以与壁层上皮细胞协调呈现抗原并参与新月体的形成。系膜细胞产生促炎细胞因子并分泌细胞外基质，导致肾小球纤维化。肾小管上皮细胞调节间质微环境，促进 T 细胞浸润和三级淋巴器官的形成。调节肾脏固有细胞的特定基因可以阻止自身免疫反应的效应物，包括自身抗体、细胞因子和免疫细胞。
狼疮肾炎的发生是多因素的，包括遗传易感性、环境触发因素和全身炎症。然而，固有肾细胞在狼疮肾炎发生中的作用越来越明确和独特。最近的研究表明，通过针对细胞的方法恢复肾脏固有细胞的功能，以预防和治疗狼疮肾炎。
