Characterizing the emergence of myeloid-derived suppressor cell subsets in a murine model of pulmonary fibrosis
Loading...
Files
Date
Authors
Publisher
Supervisors
Abstract
Myeloid-derived suppressor cells are immune cells with remarkable immunosuppressive functions. They are characterized primarily by their ability to suppress T cells, predominantly through arginase-1. There are two subgroups: polymorphonuclear and monocytic myeloid-derived suppressor cells. They play an important role in tumors, infections, and inflammatory diseases, particularly in lung diseases such as pulmonary fibrosis and asthma.
Idiopathic pulmonary fibrosis is a chronic interstitial lung disease that leads to fibrotic remodeling of lung tissue and thus to irreversible loss of lung function. Little is known about the involvement of myeloid-derived suppressor cells. We hypothesized that the immunosuppressive properties of these cells may dampen pulmonary fibrosis by inhibiting local inflammation and thus its transition to fibrosis. To test this hypothesis, we examined the generation and activity of myeloid-derived suppressor cells over a period of 21 days in a murine model of bleomycin-induced pulmonary fibrosis. Immunological, histopathological and clinical changes were investigated at days 3, 7, 14, and 21 after bleomycin challenge. Inflammation and fibrosis increased during this period. Strikingly, we found entirely different patterns of polymorphonuclear and monocytic myeloid-derived suppressor cell generation and recruitment after bleomycin exposure. This suggests that the number and activity of both subgroups varies depending on the stage of the disease. The number and suppressive activity of monocytic myeloid-derived suppressor cells appear to correlate with each other in this regard. In addition, adoptive transfer and depletion of polymorphonuclear myeloid-derived suppressor cells were performed. Adoptive transfer of polymorphonuclear myeloid-derived suppressor cells and bone marrow cells attenuated inflammation and the development of fibrosis. However, depletion of polymorphonuclear myeloid-derived suppressor cells did not lead to an exacerbation of pulmonary fibrosis. Overall, we were able to show that the generation and activity of both myeloid-derived suppressor cell subsets varies depending on the stage of the disease. Furthermore, adoptive transfer of polymorphonuclear myeloid-derived suppressor cells can improve inflammatory responses and thus the development of fibrosis in a bleomycin-induced pulmonary fibrosis model.
The significance of myeloid-derived suppressor cells was further investigated in a murine model of chronic asthma and asthma exacerbation. Asthma is one of the most common chronic lung diseases worldwide. In particular, asthma exacerbations pose a major challenge. In previous studies, our group had already shown that myeloid-derived suppressor cells play an important role in the pathogenesis of asthma and that their function can be modulated by pharmacological approaches. In addition, myeloid-derived suppressor cells were found to attenuate airway inflammation in asthma through mechanisms involving the prostaglandin E2 receptor 4 and arginase-1. Therefore, we investigated the influence of a prostaglandin E2 receptor 4 agonist and arginase-1 in a mouse model of chronic asthma and asthma exacerbation. As in the mouse model for pulmonary fibrosis, we examined lung function in vivo, the number and suppressive activity of myeloid-derived suppressor cells, histopathological changes, and the number of different T cell subsets. After systemic administration of a prostaglandin E2 receptor 4 agonist or arginase-1, we observed positive effects on inflammation in the lung. Both therapies improved lung function in vivo and led to a reduction in eosinophils and various T cell subsets. In addition, following viral infection, we observed an increase in the number and suppressive activity of myeloid-derived suppressor cells in asthma-exacerbated mice. We also observed a correlation between number and suppressive activity, similar to that seen in pulmonary fibrosis. We suggest that the positive effects in asthmatic mice are caused by a prostaglandin E2 receptor 4 agonist, myeloid-derived suppressor cells themselves, or their product arginase-1. It is conceivable that modulation of T cell proliferation is an important mechanism by which treatment with a prostaglandin E2 receptor 4 agonist or arginase-1 improves inflammation in asthmatic mice.
Overall, our studies confirm the important role of myeloid-derived suppressor cells in lung diseases such as pulmonary fibrosis and asthma. The results have led to a better understanding of the immunomodulatory role of myeloid-derived suppressor cells in both diseases. Our results also emphasize the potential efficacy of new therapeutic approaches in asthma and asthma exacerbation targeting prostaglandin E2 receptor 4, arginase-1, and myeloid-derived suppressor cells.
Review
Metadata
Contributors
Supervisor:
Dates
Issued: 2026-04-14
Relations
Is based on: 10.1096/fj.202500312RRIs based on: 10.1111/bph.17473
Faculty
FB20:Medizin
Language
en
Keywords
myeloid-derived suppressor cellspulmonary fibrosisasthma
DFG-subjects
2.21-05 - Immunologie
Funding
Funding Organisations:
Foundation for Pathobiochemistry and Molecular Diagnostics
Universities Giessen Marburg Lung Center (UGMLC) and the German Center for Lung Disease (DZL)
German Research Foundation
Open Access Publishing Funds of the Philipps University Marburg
Open Access funding by Projekt DEAL
show more
Vedder, Nora Luise: Characterizing the emergence of myeloid-derived suppressor cell subsets in a murine model of pulmonary fibrosis. : 2026-04-14.
License
Except where otherwised noted, this item's license is described as Attribution 4.0 International