Remalante-Rayco Patricia, Nakamura Akihiro
Schroeder Arthritis Institute, Spondylitis Program, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Curr Rheumatol Rep. 2024 Dec 28;27(1):9. doi: 10.1007/s11926-024-01176-3.
The canonical pathogenesis of spondyloarthritis (SpA) involves inflammation driven by HLA-B27, type 3 immunity, and gut microbial dysregulation. This review based on information presented at the SPARTAN meeting highlights studies on the pathogenesis of SpA from the past year, focusing on emerging mechanisms such as the roles of microbe-derived metabolites, microRNAs (miRNAs) and cytokines in plasma exosomes, specific T cell subsets, and neutrophils.
The induction of arthritis in a preclinical model through microbiota-driven alterations in tryptophan catabolism provides new insights as to how intestinal dysbiosis may activate disease via the gut-joint axis. Immune activation may likewise be modulated by dysregulated miRNAs and cytokines contained in plasma exosomes, which appear to influence the homeostasis of both effector T cells and regulatory T cells (Tregs). Closer examination of T cells in animal models has uncovered distinct transcriptional and functional profiles between gut and joint Tregs, as well as highly specific T cell subsets that can be targeted to induce disease modification. Newer studies including both SpA patients and preclinical models have focused on the key role of neutrophils as drivers of inflammation and new bone formation in hypoxic, inflammation-driven tissue environments, potentially through interactions with adipocytes and mesenchymal stem cells. Functional studies and high-throughput techniques using samples from SpA patients and preclinical models have significantly enhanced our understanding of SpA pathogenesis, offering new insights into the specific mechanisms of immune regulation and identifying promising therapeutic targets.
脊柱关节炎（SpA）的经典发病机制涉及由HLA - B27驱动的炎症、3型免疫反应以及肠道微生物失调。本综述基于在SPARTAN会议上展示的信息，重点介绍了过去一年中关于SpA发病机制的研究，聚焦于微生物衍生代谢物、微小RNA（miRNA）和血浆外泌体中的细胞因子、特定T细胞亚群以及中性粒细胞等新兴机制。
在临床前模型中，通过微生物群驱动的色氨酸分解代谢改变诱导关节炎，为肠道生态失调如何通过肠 - 关节轴激活疾病提供了新见解。血浆外泌体中失调的miRNA和细胞因子同样可能调节免疫激活，这些miRNA和细胞因子似乎会影响效应T细胞和调节性T细胞（Treg）的稳态。对动物模型中T细胞的进一步研究发现，肠道和关节Treg之间存在不同的转录和功能特征，以及可作为诱导疾病改善靶点的高度特异性T细胞亚群。包括SpA患者和临床前模型的最新研究都聚焦于中性粒细胞在缺氧、炎症驱动的组织环境中作为炎症和新骨形成驱动因素的关键作用，这可能是通过与脂肪细胞和间充质干细胞的相互作用实现的。使用SpA患者和临床前模型样本进行的功能研究和高通量技术显著增强了我们对SpA发病机制的理解，为免疫调节的具体机制提供了新见解，并确定了有前景的治疗靶点。
