Anti-inflammatory role of myeloid-derived suppressor cells in asthma in vivo

Abstract

Background: Asthma is a chronic lung inflammatory disease driven by over-activation of T helper 2 (Th2) cells. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their potential to suppress T-cell response. objective: To characterize MDSCs accumulation and function in allergic asthma in vivo. Methods: Allergic airway inflammation was induced in mice by ovalbumin (OVA) and house dust mite (HDM) challenge. MDSC accumulation was quantified by flow cytometry. To assess the functional in vivo impact, MDSCs were adoptively transferred intravenously (IV) or intratracheally (IT). Results: Our studies demonstrate that neutrophilic MDSCs (PMN-MDSCs) are decreased in the bronchoalveolar lavage fluid (BALF) and lungs of allergic airway inflammation in vivo. IV- or IT-transferred PMN-MDSCs were recruited to the lungs and BALF of asthmatic mice and suppressed the infiltration and local activity of Th2 and Th17 inflammatory cells. Adoptively transferred PMN-MDSCs reduced PAS-positive cells, pulmonary histopathological inflammatory scores and ameliorated airway hyperresponsiveness in asthmatic mice. Infiltration of inflammatory cells and pro-inflammatory cytokines released in BALF as well as expression of lung inflammatory transcription factors was decreased after PMN-MDSCs transfer. Arginase1, nitric oxide synthase 2, Cyclooxygenase 2 and A20 pathway were involved in the anti-inflammatory role of MDSCs in asthmatic mice. Conclusions: Collectively, our results demonstrate that MDSCs suppress Th2-dominant inflammation and improve lung function in asthmatic mice in vivo. Adoptive cellular transfer of MDSCs may represent an attractive therapeutic strategy for allergic asthma.