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Myeloid-derived suppressor cells (MDSCs) are a phenotypically heterogenous group of cells that potently suppress the immune response. A growing body of evidence supports the important role of MDSCs in a variety of lung diseases, such as asthma. However, the role of MDSCs in asthma exacerbation has so far not been investigated. Here, we studied the role of MDSCs in a murine model of influenza virus-induced asthma exacerbation. BALB/c mice were exposed to house dust mite (HDM) three times a week for a total of five weeks to induce a chronic asthmatic phenotype, which was exacerbated by additional exposure to the A/Hamburg/5/2009 hemagglutinin 1 neuraminidase 1 (H1N1) influenza virus. Induction of lung inflammatory features, production of T helper (Th) 1- and Th2- associated inflammatory cytokines in the lavage fluid and an increased airway hyper-responsiveness were observed, establishing the asthma exacerbation model. The number and activity of pulmonary M-MDSCs increased in exacerbated asthmatic mice compared to non-exacerbated asthmatic mice. Furthermore, depletion of MDSCs aggravated airway hyper-responsiveness in exacerbated asthmatic mice. These findings further denote the role of MDSCs in asthma and provide some of the first evidence supporting a potential important role of MDSCs in asthma exacerbation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 van Geffen, Lange and Kolahian.)

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent suppressive and regulative properties. MDSCs' strong immunosuppressive potential creates new possibilities to treat chronic inflammation and autoimmune diseases or induce tolerance towards transplantation. Here, we summarize and critically discuss different pharmacological approaches which modulate the generation, activation, and recruitment of MDSCs in vitro and in vivo , and their potential role in future immunosuppressive therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Geffen, Heiss, Deißler and Kolahian.)

Emerging evidence suggests a mechanistic role for myeloid-derived suppressor cells (MDSCs) in lung diseases like asthma. Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further dissected this mechanism by studying the role and therapeutic relevance of the downstream mediator prostaglandin E2 receptor 4 (EP4) in a murine model of asthma. We adoptively transferred MDSCs generated using an EP4 agonist in a murine model of asthma and studied the consequences on airway inflammation. Furthermore, pegylated human arginase-1 was used to model MDSC effector activities. We demonstrate that the selective EP4 agonist L-902,688 increased the number and suppressive activity of MDSCs through arginase-1 and nitric oxide synthase-2. These results showed that adoptive transfer of EP4-primed MDSCs, EP4 agonism alone or arginase-1 administration ameliorated lung inflammatory responses and histopathological changes in asthmatic mice. Collectively, our results provide evidence that MDSCs dampen airway inflammation in murine asthma through a mechanism involving EP4., Competing Interests: DH was employed by Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van Geffen, Deißler, Beer-Hammer, Nürnberg, Handgretinger, Renz, Hartl and Kolahian.)

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis., Competing Interests: Author DH was employed by the company Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van Geffen, Deißler, Quante, Renz, Hartl and Kolahian.)