Characterizing the Emergence of Myeloid-Derived Suppressor Cell Subsets in a Murine Model of Pulmonary Fibrosis

The immune system plays a major role in pulmonary fibrosis (PF), a devastating lung disease with limited treatment options. Myeloid-derived suppressor cells (MDSCs) are immune cells with remarkable immunosuppressive functions. We hypothesized that their anti-inflammatory activity may dampen PF by inhibiting inflammation and its transition to fibrosis. Here, we studied the emergence of both polymorphonuclear (PMN)- and monocytic (M)-MDSCs in a murine model of PF. We assessed immunological, histopathological, and clinical changes at days 3, 7, 14, and 21 following bleomycin challenge. A comprehensive overview of the role of MDSCs during the acute lung injury and chronic phase of pulmonary fibrosis is provided, along with the effects of MDSCs adoptive transfer and depletion. Inflammation and fibrosis increased over a period of 21 days after bleomycin administration. In the lung, the number of PMN-MDSCs increased, while M-MDSCs decreased over the time following bleomycin challenge. Especially, M-MDSCs showed enhanced suppressive activity on day 3 following bleomycin challenge. Adoptive transfer of PMN-MDSCs attenuated inflammation and fibrosis development. However, depletion of PMN-MDSCs did not lead to an exacerbation of PF. Our results suggest that adoptive transfer of PMN-MDSCs can ameliorate the inflammatory responses and thus the development of fibrosis in a bleomycin-induced pulmonary fibrosis model.