Myeloid Derived Suppressor Cells Attenuate Murine Allergic Airway Inflammation

Propolis is a natural product produced by bees that is primarily used in complementary and alternative medicine and has anti-inflammatory, antibacterial, antiviral, and antitumoral biological properties. Some studies have reported the beneficial effects of propolis in models of allergic asthma. In a previous study, our group showed that green propolis treatment reduced airway inflammation and mucus secretion in an ovalbumin (OVA)-induced asthma model and resulted in increased regulatory T cells (Treg) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) frequencies in the lungs, two leukocyte populations that have immunosuppressive functions. In this study, we evaluated the anti-inflammatory effects of artepillin C (ArtC), the major compound of green propolis, in the context of allergic airway inflammation. Our results show that ArtC induces in vitro differentiation of Treg cells and monocytic MDSC (M-MDSC). Furthermore, in an OVA-induced asthma model, ArtC treatment reduced pulmonary inflammation, eosinophil influx to the airways, mucus and IL-5 secretion along with increased frequency of M-MDSC, but not Treg cells, in the lungs. Using an adoptive transfer model, we confirmed that the effect of ArtC in the reduction in airway inflammation was dependent on M-MDSC. Altogether, our data show that ArtC exhibits an anti-inflammatory effect and might be an adjuvant therapy for allergic asthma.

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Polymorphonuclear myeloid‐derived suppressor cells attenuate allergic airway inflammation by negatively regulating group 2 innate lymphoid cells

Immunology ◽

10.1111/imm.13040 ◽

2019 ◽

Vol 156 (4) ◽

pp. 402-412 ◽

Cited By ~ 4

Author(s):

Yingjiao Cao ◽

Yumei He ◽

Xiangyang Wang ◽

Yongdong Liu ◽

Kun Shi ◽

...

Keyword(s):

Airway Inflammation ◽

Allergic Airway Inflammation ◽

Suppressor Cells ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Myeloid Derived Suppressor Cells ◽

Group 2

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Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4

Frontiers in Immunology ◽

10.3389/fimmu.2021.695933 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chiel van Geffen ◽

Astrid Deißler ◽

Sandra Beer-Hammer ◽

Bernd Nürnberg ◽

Rupert Handgretinger ◽

...

Keyword(s):

Prostaglandin E2 ◽

Airway Inflammation ◽

Adoptive Transfer ◽

Murine Model ◽

Inflammatory Responses ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Arginase 1 ◽

Prostaglandin E2 Receptor ◽

Nitric Oxide Synthase 2

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.

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