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

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 tis...

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Bibliographic Details
Published in:The Journal of pathology 2017-11, Vol.243 (3), p.320-330
Main 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
Format: Article
Language:English
Subjects:
Animals
carbon nanotubes
Cell Proliferation - physiology
Collagen - metabolism
immunosuppression
inflammation
Lung - pathology
lung fibrosis
Lymphocyte Activation - physiology
Mice, Inbred C57BL
Monocytes - metabolism
myeloid cells
Myeloid-Derived Suppressor Cells - cytology
Pulmonary Fibrosis - metabolism
Pulmonary Fibrosis - pathology
Receptors, CCR2 - metabolism
silica
TIMP
Transforming Growth Factor beta1 - metabolism
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Summary: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.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.4956