4 years ago

CCR2+ monocytic-Myeloid Derived Immunosuppressive Cells (M-MDSC) inhibit collagen degradation and promote lung fibrosis by producing TGF-β1

Dominique Lison, Francine Uwambayinema, Xavier Izquierdo Carerra, Doriana Ricci, Sandra Lo Re, François Huaux, Yousof Yakoub, Mathilde Chantry, Manolis Pasparakis, Lisa Brombin, Raynal Devosse, Astrid Lebrun, Mihaly Palmai-Pallag, Saloua Ibouraadaten
Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2+ monocytes possess specific immunosuppressive and pro-fibrotic 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-MDSC) because they significantly suppress T lymphocyte proliferation in vitro. M-MDSC collected from silica-treated mice also express TGF-β1, which stimulates lung fibroblasts to release TIMP-1, an inhibitor of metalloproteinase collagenolytic activity. By using LysMCreCCR2loxP/loxP mice, we show that limiting CCR2+ M-MDSC accumulation reduces pulmonary content of TGF-β1, TIMP-1 and collagen after silica treatment. M-MDSC do not differentiate into lung macrophages, granulocytes or fibrocytes during pulmonary fibrogenesis. Collectively, our data indicate that M-MDSC contribute to lung fibrosis by specifically promoting a non-degrading collagen microenvironment.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/path.4956

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