Research ArticleRheumatoid Arthritis

HBEGF+ macrophages in rheumatoid arthritis induce fibroblast invasiveness

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Science Translational Medicine  08 May 2019:
Vol. 11, Issue 491, eaau8587
DOI: 10.1126/scitranslmed.aau8587

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Malleable and manipulative macrophages

Macrophages play a critical role in rheumatoid arthritis (RA), an autoimmune disease characterized by chronic joint inflammation. Kuo et al. used single-cell RNA sequencing to identify a subset of inflammatory macrophages within human RA joints that promoted synovial fibroblast invasiveness. Testing several approved treatments for RA in ex vivo explants revealed that most drugs target inflammatory macrophages but may not resolve pathologic response. An epidermal growth factor receptor inhibitor used to treat cancer could block macrophage-fibroblast cross-talk in RA samples. This study helps elucidate macrophage phenotypes and macrophage-fibroblast cross-talk in RA, with implications for therapeutic targeting.