Spondylitis Program, Division of Rheumatology, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada.
Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Front Immunol. 2023 Jan 18;13:1102405. doi: 10.3389/fimmu.2022.1102405. eCollection 2022.
The chronic inflammatory disease ankylosing spondylitis (AS) is marked by back discomfort, spinal ankylosis, and extra-articular symptoms. In AS, inflammation is responsible for both pain and spinal ankylosis. However, the processes that sustain chronic inflammation remain unknown. Despite the years of research conducted to decipher the intricacy of AS, little progress has been made in identifying the signaling events that lead to the development of this disease. T cells, an immune cell type that initiates and regulates the body's response to infection, have been established to substantially impact the development of AS. T lymphocytes are regarded as a crucial part of adaptive immunity for the control of the immune system. A highly coordinated interaction involving antigen-presenting cells (APCs) and T cells that regulate T cell activation constitutes an immunological synapse (IS). This first phase leads to the controlled trafficking of receptors and signaling mediators involved in folding endosomes to the cellular interface, which allows the transfer of information from T cells to APCs through IS formation. Discrimination of self and nonself antigen is somatically learned in adaptive immunity. In an autoimmune condition such as AS, there is a disturbance of self/nonself antigen discrimination; available findings imply that the IS plays a preeminent role in the adaptive immune response. In this paper, we provide insights into the genesis of AS by evaluating recent developments in the function of vesicular trafficking in IS formation and the targeted release of exosomes enriched microRNAs (miRNA) at the synaptic region in T cells.
慢性炎症性疾病强直性脊柱炎 (AS) 的特征是背部不适、脊柱强直和关节外症状。在 AS 中,炎症既是疼痛的原因,也是脊柱强直的原因。然而,维持慢性炎症的过程尚不清楚。尽管多年来一直在研究以破译 AS 的复杂性,但在确定导致这种疾病发展的信号事件方面几乎没有取得进展。T 细胞是一种启动和调节身体对感染反应的免疫细胞类型,被认为对 AS 的发展有重大影响。T 淋巴细胞被认为是控制免疫系统的适应性免疫的重要组成部分。涉及抗原呈递细胞 (APC) 和调节 T 细胞活化的 T 细胞的高度协调相互作用构成了免疫突触 (IS)。这个第一阶段导致参与折叠内体的受体和信号介质的受控贩运到细胞界面,这允许通过 IS 形成将信息从 T 细胞传递到 APC。适应性免疫中通过体细胞学习来区分自身和非自身抗原。在 AS 等自身免疫性疾病中,存在自身/非自身抗原识别障碍;现有发现表明,IS 在适应性免疫反应中起着突出的作用。在本文中,我们通过评估 IS 形成中囊泡运输的功能以及在 T 细胞突触区富含 miRNA 的外泌体的靶向释放的最新进展,深入了解 AS 的发病机制。