{
  "abstract": "Objective Anaemia is common in rheumatoid arthritis (RA), but the role of erythroid-lineage cells is unclear. We investigated the function of CD45 + erythroid progenitor cells (CD45+ EPCs) in RA.Methods We analysed CD45 + EPC frequency in patients with RA and mice with collagen-induced arthritis (CIA). Transcriptomics, functional studies and mechanistic assays (Transwell and dual-luciferase reporter assays, chromatin immunoprecipitation followed by quantitative PCR) were used. Therapeutic potential was tested in RA synovial organoids and via splenectomy/adoptive transfer in mice with CIA.Results CD45 + EPCs were expanded in RA circulation and CIA mouse spleens, correlating positively with disease activity and negatively with haemoglobin. They displayed an immunosuppressive transcriptome, enriched for transforming growth factor (TGF)-β and chemokine signalling. RA-derived CD45+ EPCs showed enhanced proliferation and TGF-β/reactive oxygen species production. High C-C Motif Chemokine Receptor 2 (CCR2) expression made them susceptible to recruitment by macrophage-derived C-C Motif Chemokine Ligand 2 (CCL2). In RA synovial organoids, CD45+ EPCs suppressed growth and inflammation via TGF-β, while organoid-conditioned media promoted their migration via CCL2. Recruited CD45+ EPCs suppressed M1 and promoted M2-like macrophage polarisation. The transcription factor SPI1 was upregulated in RA CD45+ EPCs, bound the TGFB1 promoter and drove TGF-β production. In vivo, splenectomy worsened CIA, whereas adoptive transfer of CD45+ EPCs ameliorated arthritis.Conclusion We identify CD45 + EPCs as a novel, SPI1-driven immunosuppressive population in RA. Recruited via the CCR2-CCL2 axis, they attenuate inflammation by modulating macrophages through SPI1/TGF-β signalling, revealing a new immunoregulatory axis and potential therapeutic targets.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Wei-Hang Zhu"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Man-Li Wang"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Xia Meng"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Shu-Yuan Zhong"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Yan Liu"
    },
    {
      "affiliations": [
        "Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Yun-Feng Pan"
    }
  ],
  "title": "Transcription factor SPI1 drives immunosuppressive CD45+ erythroid progenitor cells to ameliorate rheumatoid arthritis",
  "uid": "14365f81-9fec-5529-a609-3b0005a8840e"
}