Department of Nephrology, Limassol General Hospital, Limassol, Cyprus and Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Rheumatology, Clinical Immunology and Allergy, University of Crete Medical School, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Greece; University Hospital of Iraklio, Iraklio, Greece.
Clin Immunol. 2020 Jul;216:108445. doi: 10.1016/j.clim.2020.108445. Epub 2020 Apr 25.
Recent progress has highlighted the involvement of a variety of innate and adaptive immune cells in lupus nephritis. These include activated neutrophils producing extracellular chromatin traps that induce type I interferon production and endothelial injury, metabolically-rewired IL-17-producing T-cells causing tissue inflammation, follicular and extra-follicular helper T-cells promoting the maturation of autoantibody-producing B-cells that may also sustain the formation of germinal centers, and alternatively activated monocytes/macrophages participating in tissue repair and remodeling. The role of resident cells such as podocytes and tubular epithelial cells is increasingly recognized in regulating the local immune responses and determining the kidney function and integrity. These findings are corroborated by advanced, high-throughput genomic studies, which have revealed an unprecedented amount of data highlighting the molecular heterogeneity of immune and non-immune cells implicated in lupus kidney disease. Importantly, this research has led to the discovery of putative pathogenic pathways, enabling the rationale design of novel treatments.
最近的研究进展强调了多种固有免疫和适应性免疫细胞参与狼疮肾炎。这些细胞包括产生细胞外染色质陷阱的活化中性粒细胞，诱导 I 型干扰素产生和血管内皮损伤；代谢重编程的产生 IL-17 的 T 细胞引起组织炎症；滤泡和滤泡外辅助 T 细胞促进产生自身抗体的 B 细胞的成熟，这也可能维持生发中心的形成；以及替代活化的单核细胞/巨噬细胞参与组织修复和重塑。越来越多的研究发现，驻留细胞（如足细胞和肾小管上皮细胞）在调节局部免疫反应和决定肾脏功能和完整性方面起着重要作用。这些发现得到了高通量基因组研究的支持，这些研究揭示了大量前所未有的数据，突出了参与狼疮性肾病的免疫和非免疫细胞的分子异质性。重要的是，这项研究导致了潜在致病途径的发现，使新型治疗方法的合理设计成为可能。
