Passive transfer of tumour-derived MDSCs inhibits asthma-related airway inflammation

Abstract

Myeloid-derived suppressor cells (MDSCs), a heterogeneous population including myeloid progenitor and immature myeloid cells, are known to inhibit T cell responses. The issue of whether tumour-derived MDSCs regulate the immune response in an asthma environment is currently unclear. Here, we have reported that tumour-derived MDSCs shift the balance back to normal in a Th2-dominant asthmatic environment. In an ovalbumin (OVA)-induced mouse asthma model, injected tumour-derived MDSCs were recruited to the lungs of asthmatic mice by CC chemokine ligand 2 (CCL2). MDSCs transferred into asthmatic mice via i.v. injection suppressed the infiltration of inflammatory cells into the lung, the Th2 cytokine, IL-4, concentration in bronchial lavage fluid and the serum level of OVA-specific IgE. Increased TGF-β1 production in the lung was detected after transfer of MDSCs. The inhibitory effects of MDSCs were reversed upon treatment with an anti-TGF-β1 antibody, suggesting dependence of these activities on TGF-β1. Our findings imply that tumour-derived MDSCs inhibit the Th2 cell-mediated response against allergen in a TGF-β1-dependent manner. Based on the collective results, we propose that asthma may be effectively targeted using a novel MDSC-based cell therapy approach.