Synovial Tissue Macrophage Heterogeneity in Rheumatoid Arthritis

Synovial tissue macrophages are critical orchestrators in the pathogenesis of rheumatoid arthritis, comprising a heterogeneous population of subsets. Despite the crucial role of these cells in disease, the relative contribution of specific macrophage subsets in the evolution and perpetuation of inflammation in RA has yet to be fully elucidated. Recent technological advances have allowed for a more detailed examination of synovial tissue macrophages, developmentally, functionally, and spatially. Single-cell technologies, for example, have revealed a spectrum of myeloid subsets existing in the synovium in health and disease, with different phenotypic characteristics and functions. This review will explore recent findings in this area. We will review the ontogeny of tissue macrophages, their metabolic demands, and their crosstalk with other key cell types within the synovium, the key site of pathology and immune dysregulation in RA. The contributions of synovial tissue macrophages in shaping the inflammatory environment in RA will also be reviewed, and conversely, we will touch upon mechanisms by which the local environment influences the development of synovial tissue macrophages. A better understanding of these domains will be crucial to the identification of novel therapeutics targeting macrophages in RA.