25 Role of Myeloid Derived Suppressor Cells in Asthma

BACKGROUND: We know that a heterogeneous group of myeloid cells termed myeloid derived suppressor cells (MDSC) accumulate in almost all pathological conditions, which elicit an inflammatory signal. The exact role played by these cells in asthma is not known. In this study we investigated the function and role of these cells in asthma. METHODS: Accumulation of MDSC and other subsets of myeloid cells were analyzed from peripheral blood mononuclear cells from patients with non-severe asthma (FEV(1)) >60) and severe asthma (FEV(1) <60) by multicolor-flowcytometry and compared to healthy controls. Allergic mouse models were used to determine the role of microRNA-142 (miR-142) in regulation and expansion of MDSC. RESULTS: There is a significant increase in the proportion of MDSC in severe versus non-severe asthmatics and controls, corresponding to a decrease in myeloid dendritic cells. Allergic mice had significant increased levels of MDSC expansion which were associated with increased levels of IL-6 and downregulation of miR-142. miR-142 overexpression induced MDSC differentiation. CONCLUSIONS: An accumulation of MDSC is associated with severe asthma in humans and mice. In an allergic mouse model, IL-6 levels increase. miR-142 may play an important role in regulation and differentiation of MDSC, leading to altered immunity.