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- Title
CCR2<sup>+</sup> monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-β1.
- Authors
Lebrun, Astrid; Lo Re, Sandra; Chantry, Mathilde; Izquierdo Carerra, Xavier; Uwambayinema, Francine; Ricci, Doriana; Devosse, Raynal; Ibouraadaten, Saloua; Brombin, Lisa; Palmai‐Pallag, Mihaly; Yakoub, Yousof; Pasparakis, Manolis; Lison, Dominique; Huaux, François
- Abstract
Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2+ monocytes have specific immunosuppressive and profibrotic functions. CCR2+ monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice. These tissue monocytes are defined as monocytic myeloid-derived suppressor cells (M-MDSCs) because they significantly suppress T-lymphocyte proliferation in vitro. M-MDSCs collected from silica-treated mice also express transforming growth factor (TGF)-β1, which stimulates lung fibroblasts to release tissue inhibitor of metalloproteinase (TIMP)-1, an inhibitor of metalloproteinase collagenolytic activity. By using LysMCreCCR2 loxP/ loxP mice, we show that limiting CCR2+ M-MDSC accumulation reduces the pulmonary contents of TGF-β1, TIMP-1 and collagen after silica treatment. M-MDSCs do not differentiate into lung macrophages, granulocytes or fibrocytes during pulmonary fibrogenesis. Collectively, our data indicate that M-MDSCs contribute to lung fibrosis by specifically promoting a non-degrading collagen microenvironment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Publication
Journal of Pathology, 2017, Vol 243, Issue 3, p320
- ISSN
0022-3417
- Publication type
Article
- DOI
10.1002/path.4956