{
  "abstract": "Objective To characterise phenotype and functional profibrotic M2 markers in circulating monocytes and cultured monocyte-derived macrophages (MDMs) from systemic sclerosis (SSc) patients (pts) with progressive interstitial lung disease (ILD) (prog-ILD), non-progressive ILD (no-prog-ILD) and without ILD (no-ILD).Methods Fifty-five SSc pts and 20 age-matched healthy controls were evaluated. In 36 SSc pts, circulating monocytes expressing toll-like receptor-4 (TLR4, M1 marker) and M2 phenotype markers (CD204, CD206, CD163) were detected by flow cytometry. Moreover, MDMs of 29 SSc pts were analysed by quantitative real-time PCR and Western blotting for gene expression and protein synthesis with regard to the production of profibrotic mediators: transforming growth factor-ß1 (TGFß1), Mer tyrosine kinase receptor (MerTK) and arginase-1 (ARG1). Interleukin-6 and 4 (IL6, IL4), as well as C-C motif chemokine ligand 2 and 18 (CCL2/MCP1 and CCL18) from culture medium, were evaluated by enzyme-linked immunosorbent assay (ELISA).Results Prog-ILD SSc pts showed a higher percentage of TLR4 +CD204+CD206+CD163+ monocytes versus no-prog-ILD, and significantly higher compared with no-ILD SSc pts.Interestingly, MDMs from prog-ILD SSc pts showed a significantly higher gene expression and protein synthesis of TGFβ1, and a significantly higher protein synthesis of MerTK, CD206, IL4 and CCL18 compared with no-prog-ILD SSc pts. Finally, gene expression and protein synthesis of TGFβ1, TLR4, CD206, CD163, ARG1, MerTK and IL6 were significantly increased in prog-ILD SSc versus no-ILD SSc MDMs.Conclusions Cultured MDMs from circulating monocytes in SSc pts with prog-ILD show markedly increased profibrotic biomarkers and mediator expression, indicating an enhanced fibrotic phenotype compared to non-prog and no-ILD SSc pts.",
  "authors": [
    {
      "affiliations": [
        "Department of Rheumatology and Internal Medicine, University Hospital Ghent, Ghent, Flanders, Belgium",
        "Unit for Molecular Immunology and Infammation, Flemish Institute for Technological Research, Mol, Flanders, Belgium",
        "Department of Internal Medicine, Ghent University Hospital, University of Ghent, Ghent, Belgium"
      ],
      "name": "Vanessa Smith"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy"
      ],
      "name": "Stefano Soldano"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "Department of Experimental Medicine (DIMES), University of Genoa, Genova, Italy"
      ],
      "name": "Rosanna Campitiello"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy"
      ],
      "name": "Paola Montagna"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy"
      ],
      "name": "Andrea Cere"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "Department of Experimental Medicine (DIMES), University of Genoa, Genova, Italy"
      ],
      "name": "Elvis Hysa"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy"
      ],
      "name": "Tamara Vojinovic"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy"
      ],
      "name": "Carmen Pizzorni"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy"
      ],
      "name": "Sabrina Paolino"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy"
      ],
      "name": "Alberto Sulli"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy"
      ],
      "name": "Emanuele Gotelli"
    },
    {
      "affiliations": [
        "Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialities (Di.M.I.), University of Genoa, Genoa, Liguria, Italy",
        "IRCCS Ospedale Policlinico San Martino, Genoa, Liguria, Italy"
      ],
      "name": "Maurizio Cutolo"
    }
  ],
  "title": "Circulating monocytes from systemic sclerosis patients with progressive interstitial lung disease preferentially express M2 phenotype markers: in vitro and ex vivo study",
  "uid": "3bac09da-ab3d-580d-9cae-4d234cd460a8"
}