Der Einfluss von IL-10 und IL-17 auf myeloide Suppressorzellen in vivo im murinen Asthma-Modell

Vetter, Charlotte

Thesis

Open Access

Der Einfluss von IL-10 und IL-17 auf myeloide Suppressorzellen in vivo im murinen Asthma-Modell

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Primary dcv.pdf (20.18 MB)

Date

2026-04-14

Authors

Vetter, Charlotte

Supervisors

Person

Kolahian, Saeed

Person

Schmeck, Bernd

Abstract

The two studies presented in this cumulative dissertation explored the impact of IL-10 and IL-17 deficiency and therapy with EP4 agonist and Arginase-1 on MDSCs in different HDM-induced murine asthma models. MDSCs are immature immune cells that suppress T cell responses. While originally studied in cancer research, growing evidence suggests MDSCs may serve as a new therapeutic target for lung diseases like asthma. To further elucidate their immunosuppressive mechanisms, these studies focused on key regulatory factors and their effect in murine asthma models. The first study (Vetter et al., 2024) examined the role of the interleukins IL-10 and IL-17 by analyzing lung inflammatory features, MDSC numbers, and activity in Il10-/- and Il17- /- mice in vitro and in vivo in an acute asthma model. In vitro, Il10-/- mice showed increased PMN-MDSC numbers compared to wild type mice, while neither IL-10 nor IL-17 deficiency affected suppressive activity of MDSCs. In asthmatic Il17-/- mice, M-MDSC numbers and suppressive activity were reduced, whereas lung function was more impaired compared to asthmatic Il10-/- mice. These findings suggest a crucial role of IL- 17 in MDSC mediated anti-inflammatory effects in asthma and provide a foundation for further research into its underlying mechanisms. The second study (Lange et al., 2025) built upon previous research from our group by analyzing the effects of systemic EP4 agonist and Arginase-1 treatment in a chronic asthma model and an influenza virus-induced asthma exacerbation model. MDSC numbers and activity, lung inflammatory features, and T cells subsets were examined. While MDSC numbers and activity remained unaffected by EP4 agonist or Arginase-1 therapy, both treatments led to a reduction in eosinophil numbers in the BALF of asthmatic mice. In asthma exacerbated mice, lung function showed slight improvement, and several T cell subsets were reduced following EP4 agonist and Arginase-1 treatment. These findings further confirm the anti-asthmatic effects of EP4 agonist and Arginase-1 therapy. Taken together, both studies provide new insights into MDSC-mediated immune regulation in asthma and lay the groundwork for future research into their precise mechanisms, offering potential for novel asthma therapies.