Spatial reconstruction of joint inflammation in rheumatoid arthritis
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Inflammation is a complex interplay between immune cells and tissue stromal cells that leads to pathology and end-organ damage. Deconstructing inflammation using single-cell technologies has revealed previously underappreciated cellular heterogeneity in organ tissues in chronic inflammatory diseases such as rheumatoid arthritis.
However, the structural and organization principles of joint inflammation remain poorly understood due to the lack of spatial contexture and molecular insights behind infiltrating immune cells within affected joints. To gain spatial insights into organizational principles underlying joint inflammation in rheumatoid arthritis, our group performed spatial transcriptomic profiling of rheumatoid arthritic joint tissues. By integrating transcriptomic profiles of individual cells with spatial profiles, we identified distinct spatially-restricted zones that correspond to unique inflammation neighborhoods. These spatial neighborhoods are transcriptionally unique and compromised of distinct immune and stromal cells, suggesting that immune cells, rather than dispersed in random locations, reside in specialized, anatomical neighborhoods. Understanding molecular control of inflammation zonation will be critical in elucidating biological insights and novel therapeutic targets in rheumatoid arthritis.