CCR2+ monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-β1.

Lebrun, Astrid;Lo Re, Sandra;Chantry, Mathilde;Izquierdo Carrera, Xavier;Huaux, François;et.al.
(2017) Journal of Pathology — Vol. 243, n° 3, p. 320-330 (2017)

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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 LysMCreCCR2loxP/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.
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Lebrun, A., Lo Re, S., Chantry, M., Izquierdo Carrera, X., Uwambayinema, F., Ricci, D., Devosse, R., Ibouraadaten, S., Brombin, L., Palmai-Pallag, M., Yakoub, Y., Pasparakis, M., Lison, D., & Huaux, F. (2017). CCR2+ monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-β1. Journal of Pathology, 243(3), 320-330. https://doi.org/10.1002/path.4956 (Original work published 2017)