Rheumatoid arthritis: basic mechanisms in joints

Rheumatoid arthritis (RA) is a destructive polyarthritis which mostly starts in the small joints of the hands and feet. In the course of the disease, more proximal joints also become involved. The progressive destruction of joint structures is mediated by the chronically inflamed, hyperplasic synovial tissue, which attaches to and degrades the adjacent joint cartilage. Typical changes of the RA synovium are increased cellularity in the synovial lining and sublining layer, including vascularization, giant cell formation, and immigration of immune cells. The inflammatory cell infiltrate comprises macrophages, monocytes, dendritic cells, T cells, B cells, plasma cells, innate lymphoid cells, and mast cells. These cells together with resident stromal cells (synovial fibroblasts) form a complex network and maintain inflammatory and destructive processes via the secretion of various cytokines and chemokines. Intracellularly, cytokine-activated receptor signalling is mediated via protein kinase-dependent signalling pathways, such as mitogen-activated protein kinases and Janus kinase, which leads to the activation of transcription factors and thus changes in the transcriptional programme. Gene transcription is additionally modified by epigenetic mechanisms and post-transcriptionally by microRNA.