Manning Julia E, Lewis Jonathan W, Marsh Lucy-Jayne, McGettrick Helen M
Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
Front Cell Dev Biol. 2021 Mar 9;9:635102. doi: 10.3389/fcell.2021.635102. eCollection 2021.
The inappropriate accumulation and activation of leukocytes is a shared pathological feature of immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Cellular accumulation is therefore an attractive target for therapeutic intervention. However, attempts to modulate leukocyte entry and exit from the joint have proven unsuccessful to date, indicating that gaps in our knowledge remain. Technological advancements are now allowing real-time tracking of leukocyte movement through arthritic joints or joint constructs. Coupling this technology with improvements in analyzing the cellular composition, location and interactions of leukocytes with neighboring cells has increased our understanding of the temporal dynamics and molecular mechanisms underpinning pathological accumulation of leukocytes in arthritic joints. In this review, we explore our current understanding of the mechanisms leading to inappropriate leukocyte trafficking in inflammatory arthritis, and how these evolve with disease progression. Moreover, we highlight the advances in imaging of human and murine joints, along with multi-cellular joint constructs that have led to our current knowledge base.
白细胞的不适当积累和活化是免疫介导的炎症性疾病（IMIDs）如类风湿性关节炎（RA）和银屑病关节炎（PsA）的共同病理特征。因此，细胞积累是治疗干预的一个有吸引力的靶点。然而，迄今为止，调节白细胞进出关节的尝试已被证明是不成功的，这表明我们的知识仍存在空白。技术进步现在允许实时追踪白细胞通过关节炎关节或关节构建体的运动。将这项技术与分析白细胞的细胞组成、位置以及与邻近细胞的相互作用方面的改进相结合，增加了我们对关节炎关节中白细胞病理积累的时间动态和分子机制的理解。在这篇综述中，我们探讨了目前对炎症性关节炎中导致白细胞异常运输的机制的理解，以及这些机制如何随疾病进展而演变。此外，我们强调了人类和小鼠关节成像以及多细胞关节构建体方面的进展，这些进展形成了我们目前的知识库。
