The impact of IL-10 and IL-17 on myeloid-derived suppressor cells in vitro and in vivo in a murine model of asthma.

Abstract

Myeloid-derived suppressor cells (MDSCs) hold promise for clinical applications due to their immunosuppressive properties, particularly in the context of inflammation. In the present study, the number and immunosuppressive activity of MDSCs isolated from naïve Il10-/-, Il17-/-, and WT mice as control, as well as from house dust mite extract (HDM)-induced asthmatic Il10-/- and Il17-/- mice, were investigated. IL-10 deficiency increased the number of polymorphonuclear (PMN)-MDSCs in the lung, spleen, and bone marrow, without concurrent impairment of their suppressive activity in vitro. In the asthma model, the IL-17 knockout was concomitant with a lower number and activity of monocytic (M)-MDSCs and an altered inflammatory reaction with impaired lung function. Additionally, we found a higher baseline inflammation of the Il17-/- mice in the lung, manifested in increased airway resistance. We conclude that the impact of IL-10 and IL-17 deficiency on MDSCs differs in the context of inflammation. Accordingly, the in vitro experiments demonstrated an increased number of PMN-MDSCs across tissues in Il10-/- mice, which indicates that IL-10 might serve a pivotal role in preserving immune homeostasis under physiological circumstances. In the context of HDM-induced airway inflammation, IL-17 was found to be an important player in the suppression of pulmonary inflammation and regulation of M-MDSCs.