Synovial Tissue: Cellular and Molecular Phenotyping.

Abstract

This review provides a summary of recent molecular findings that have refined our understanding of the cell types that constitute human synovial tissue, particularly in patients with rheumatoid arthritis (RA). Recent advances in high-dimensional and single-cell assays have elucidated upwards of 20 cell subsets in the RA synovium. This includes novel fibroblast populations and lymphocyte phenotypes, which in many cases exhibit features that have not been found in other tissues thus far. Molecular profiling studies over the past several years have rapidly generated a comprehensive and detailed outline of the cellular phenotypes in synovial tissue affected by RA. Molecular features of these newly identified cell subsets immediately represent reasonable therapeutic targets and provide the opportunity to design the most clinically relevant mechanistic experiments. Broadly speaking, the ~ 20 cell types thus far identified in RA synovium seem to be fairly well conserved across patients, despite extensive heterogeneity in patient clinical features, stage of disease, and treatment responses. Thus, a next phase in molecular profiling may benefit from quantifying patient samples in terms of the ratios of cell types, with the rationale that certain cellular interactions will predominate in an individual and medications targeting these interactions may be more efficacious for that individual. Such cellular profiling in tissues combined with studies examining how the compendium of these cells interact in their three-dimensional tissue ultrastructures will be important in understanding how collectively these cells drive the disease process and ultimately how best to treat patients.