Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis

By S. Alivernini, L. MacDonald, A. Elmesmari, Samuel Finlay, B. Tolusso, M. Gigante, L. Petricca, C. Di Mario, L. Bui, S. Perniola and 21 more. Nature Medicine, 2020

595 citations recorded by the source corpus.

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterized by different frequencies of nine discrete phenotypic clusters within four distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas, combined with deep-phenotypic, spatial and functional analyses of synovial biopsy fluorescent activated cell sorted STMs, revealed two STM subpopulations (MerTKposTREM2high and MerTKposLYVE1pos) with unique remission transcriptomic signatures enriched in negative regulators of inflammation. These STMs were potent producers of inflammation-resolving lipid mediators and induced the repair response of synovial fibroblasts in vitro. A low proportion of MerTKpos STMs in remission was associated with increased risk of disease flare after treatment cessation. Therapeutic modulation of MerTKpos STM subpopulations could therefore be a potential treatment strategy for RA. Multiple subpopulations of synovial tissue macrophages with varied transcriptional, phenotypic and functional features may contribute to disease flare and tissue repair in patients with active rheumatoid arthritis and patients in clinical remission.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/ea9bb7ba5bc39b6087ed1bd72114547a98ec8cdf

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

  1. QUAN LIU
  2. Haizhao Xu
  3. L. Rao
  4. Qiong Jiang
  5. Abdullah Saeed
  6. G. Xiao
  7. Shanze Chen
  8. Yanhong Duo

Citations in the corpus