Summary
This cumulative dissertation investigates the influence of interleukin-10 (IL-10) and interleukin-17 (IL-17) signaling on myeloid-derived suppressor cells (MDSCs). For this purpose, MDSCs isolated from IL-10-, IL-17-deficient and wildtype mice were studied in regard to generation, distribution, and functional properties in distinct inflammatory contexts.
The first study examines how the complete absence of IL-10 or IL-17 affects MDSC development and activity in vitro and in vivo. Despite its well-established anti-inflammatory role, IL-10 deficiency was linked with increased numbers of polymorphonuclear MDSCs (PMN-MDSCs) in multiple organs such as lung, spleen and bone marrow. Building upon these in vitro findings, a murine model of house dust mite (HDM)-induced asthma was utilized. In this inflammatory context, IL-17 deficiency resulted in reduced number of monocytic MDSCs (M-MDSCs), impaired inflammatory responses, and decreased lung function, highlighting the cytokine’s significance for MDSCs and airway inflammation.
The second study looks into the function of MDSCs in pulmonary fibrosis using a bleomycin- induced pulmonary fibrosis model. Although not directly involving IL-10- or IL-17-deficient mice, this study provides additional insights into MDSC function during the transition from chronic inflammation to fibrosis. The functional modulation of MDSCs revealed a protective effect, with adoptive transfer of PMN-MDSCs improving disease outcomes by attenuating inflammation and fibrosis, while MDSC depletion exacerbated pathology to some extent.
Together, these studies specify how IL-10 and IL-17 signaling deficiencies affects MDSC dynamics, as well as how MDSCs influence disease progression in inflammatory and fibrotic lung conditions. These findings deepen the understanding of cytokine-MDSC interaction and may contribute to the development of future therapeutic strategies targeting dysregulated IL-10/IL-17 pathways and MDSC function in chronic lung diseases such as asthma and lung fibrosis.
