A Mechanistic Cellular Atlas of the Rheumatic Joint

Abstract

Rheumatoid Arthritis (RA) is an autoimmune disease of unknown aetiology involving complex interactions between environmental and genetic factors. Its pathogenesis is suspected to arise from intricate interplays between signalling, gene regulation and metabolism, leading to synovial inflammation, bone erosion and cartilage destruction in the patients’ joints. In addition, the resident synoviocytes of macrophage and fibroblast types can interact with innate and adaptive immune cells and contribute to the disease’s debilitating symptoms. Therefore, a detailed, mechanistic mapping of the molecular pathways and cellular crosstalks is essential to understand the complex biological processes and different disease manifestations. In this regard, we present the RA-Atlas, an SBGN-standardized, interactive, manually curated representation of existing knowledge related to the onset and progression of RA. This state-of-the-art RA-Atlas includes an updated version of the global RA-map covering relevant metabolic pathways and cell-specific molecular interaction maps for CD4+ Th1 cells, fibroblasts, and M1 and M2 macrophages. The molecular interaction maps were built using information extracted from published literature and pathway databases and enriched using omic data. The RA-Atlas is freely accessible on the webserver MINERVA (https://ramap.uni.lu/minerva/), allowing easy navigation using semantic zoom, cell-specific or experimental data overlay, gene set enrichment analysis, pathway export or drug query.