The hidden face of monocytes in particle-induced lung fibrosis and mesothelioma
(2016) 8th meeting of the Immunotoxicology and Chemical Allergy Specialty Section (ITCASS) from EUROTOX — Location: Paris (17.November.2016)
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- Abstract
- Monocytes infiltrating damaged tissues are predominantly viewed as macrophage progenitor cells. Here, we show that tissue monocytes possessing specific immunosuppressive and pro-fibrotic functions not related to macrophage accumulate during lung fibrogenesis. CD11b+Gr1+Ly6C+CCR2+ monocytes are acutely recruited in lungs before the onset of particle-induced fibrosis in mice. These tissue monocytes are defined as monocytic Myeloid-Derived Suppressor Cells (M-MDSC) because they significantly suppress T lymphocyte proliferation by producing arginase-1. M-MDSC also express TGF-b1 that stimulates lung fibroblasts to release TIMP-1, an inhibitor of metalloproteinase collagenolytic activity. By using LysMCreCCR2loxP/loxP mice, we show that M-MDSC depletion significantly reduces pulmonary content of TGF-β1, TIMP-1 and collagen after particles. Importantly, M-MDSC do not differentiate in lung macrophages, granulocytes or fibrocytes during pulmonary fibrogenesis. Collectively, our data indicate that arginase-producing M-MDSC contribute to lung fibrosis by specifically producing TGF-β1 and promoting a non-degrading collagen microenvironment.
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Huaux, F. (2016). The hidden face of monocytes in particle-induced lung fibrosis and mesothelioma. 8th meeting of the Immunotoxicology and Chemical Allergy Specialty Section (ITCASS) from EUROTOX, Paris. https://hdl.handle.net/2078.5/229414