Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Leading Medical Research Core Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Clin Immunol. 2024 May;262:110168. doi: 10.1016/j.clim.2024.110168. Epub 2024 Mar 7.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder impacting various organs, notably prevalent in women of reproductive age. This review explores the involvement of a disintegrin and metalloproteinases (ADAMs) in SLE pathogenesis. Despite advancements in understanding SLE through genome and transcriptome studies, the role of ADAMs in post-translational regulations remains insufficiently explored. ADAMs, transmembrane proteins with diverse functions, impact cell adhesion, migration, and inflammation by shedding cell surface proteins, growth factors, and receptors. Notably, ADAM9 is implicated in Th17 cell differentiation, which is crucial in SLE pathology. ADAM10 and ADAM17 play pivotal roles in T-cell biology, influencing immune cell development and differentiation. Elevated soluble ADAM substrates in SLE patients serve as potential biomarkers correlating with disease activity. Targeting ADAMs or their substrates offers promising therapeutic avenues for SLE management and treatment enhancement.
系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，影响多个器官，尤其在育龄妇女中较为常见。本综述探讨了解整合素金属蛋白酶（ADAMs）在 SLE 发病机制中的作用。尽管通过基因组和转录组研究对 SLE 的认识有所提高，但 ADAMs 在翻译后调控中的作用仍未得到充分探索。ADAMs 是具有多种功能的跨膜蛋白，通过脱落细胞表面蛋白、生长因子和受体来影响细胞黏附、迁移和炎症。值得注意的是，ADAM9 参与了 Th17 细胞分化，这在 SLE 病理中至关重要。ADAM10 和 ADAM17 在 T 细胞生物学中发挥关键作用，影响免疫细胞的发育和分化。SLE 患者中可溶性 ADAM 底物的升高可作为潜在的生物标志物，与疾病活动相关。靶向 ADAMs 或其底物为 SLE 的管理和治疗提供了有前途的途径。
