Vesicular traffic-mediated cell-to-cell signaling at the immune synapse in Ankylosing Spondylitis

Abstract

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.

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis

“…As of October 2022, only a handful of AS-related GEO datasets met these requirements. These datasets contain blood samples, synovial biopsies, and mesenchymal stem cells, but not exosomes 50. Regarding the involvement of exosomes in other rheumatic diseases, we evaluated available datasets from the GEO database for all rheumatic diseases, and exosomes and miRNA, including only series analysed in Homo sapiens and Mus musculus by expression profiling by array or sequencing.…”

Shedding Light on the Role of ERAP1 in Axial Spondyloarthritis

“…However, the mechanisms underlying this chronic inflammation remain unclear. Despite years of research on the complexities of axSpA, little progress has been made in identifying the signaling events that lead to disease development [4].…”