Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies

The recent application of single-cell genomics to the investigation of immune-mediated arthritis has resulted in an explosion of information, including the discovery of lymphocyte, myeloid and fibroblast cell subsets proposed to be pathogenic. A challenge in the field is how to leverage these exciting but largely descriptive and correlative datasets to gain insights into causality and mechanisms of disease. In this Perspective, I describe emerging data and discuss ideas about how spatial transcriptomics, ex vivo mechanistic and organoid studies, and improved use of animal models based on human disease data can advance the understanding of immune-mediated arthritis pathogenesis, with a focus on rheumatoid arthritis. These insights can form the basis for designing new therapeutic strategies and implementing clinical trials. The concepts and approaches described here for arthritis may have broader applicability to other tissues and immune-mediated diseases.