| First Author | Lebrun A | Year | 2017 |
| Journal | J Pathol | Volume | 243 |
| Issue | 3 | Pages | 320-330 |
| PubMed ID | 28799208 | Mgi Jnum | J:245231 |
| Mgi Id | MGI:5915987 | Doi | 10.1002/path.4956 |
| Citation | Lebrun A, et al. (2017) CCR2+ monocytic myeloid-derived suppressor cells (M-MDSCs) inhibit collagen degradation and promote lung fibrosis by producing transforming growth factor-beta1. J Pathol 243(3):320-330 |
| abstractText | 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)-beta1, 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-beta1, 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 (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
