Passive transfer of lipopolysaccharide-derived myeloid-derived suppressor cells inhibits asthma-related airway inflammation

H.-Z. Fan, H.-P. Yu, R. Yu, Y. Zhang, H.-J. Deng, X. Chen

Department of Respiratory Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. gaoyiyi126@126.com

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• Respiratory Medicine

OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) have recently been implicated in the pathogenesis of asthma through inhibiting T cell response. However, the issue of whether Lipopolysaccharide (LPS)-derived MDSCs regulate the immune response in an asthma environment is currently unclear. We sought to characterize the pathogenic function of various subtypes of MDSCs in asthma mediated by ovalbumin in mice model, in order to show that LPS-induced MDSCs can shift the balance back to normal in a Th2-dominant asthmatic environment.

MATERIALS AND METHODS: Subgroups of MDSCs with Ly6C+Ly6G+, Ly6C–Ly6G+, Ly6C+Ly6G– or Ly6C–Ly6G– expression were isolated by flow cytometry and were co-cultured with spleen lymphocytes. The proportion of Th1, Th2, or Treg cells in the treated spleen lymphocytes were analyzed by flow cytometry. In an ovalbumin (OVA)-induced mouse asthma model, mice were intravenously injected (tail vein) by MDSCs with specific marker, then the lung function and tissue pathology, IL-4 content in bronchoalveolar lavage fluid (BALF) and peripheral blood, and proportion of Th1, Th2, or Treg cells in peripheral blood were analyzed.

RESULTS: Ly6C+Ly6G+ MDSCs transferred into asthmatic mice via intravenous injection suppressed the infiltration of inflammatory cells into the lung and Th2 cytokine in BALF and blood. We observed a significant increase of Treg cells in the spleen lymphocytes co-cultured with Ly6C+Ly6G+, Ly6C–Ly6G+, Ly6C+Ly6G–, Ly6C–Ly6G– or CD11b+ MDSCs. The adoptive transfer of Ly6C+Ly6G+, Ly6C–Ly6G+, CD11b+ MDSCs resulted in decrease of Penh, total cell number, eosinophil and neutrophil percentage in BALF, and concentration of IL-4 in BALF and serum, thus improving the inflammatory injury, histopathology and lung function in the mice with asthma. The up-regulation of the Th1/Th2 ratio and Treg frequency were observed after adoptive transfer of Ly6C+Ly6G+, Ly6C−Ly6G+, Ly6C+Ly6G–, Ly6C−Ly6G− and CD11b+ MDSCs.

CONCLUSIONS: The LPS-derived MDSCs with specific markers were able to suppress natural inflammatory response and improve inflammatory injury through reversing Th1/Th2 ratio, increasing Treg proportion and decreasing IL-4 concentration. These findings imply that LPS-derived MDSCs inhibit Th2 cell-medicated response against allergen. We propose that asthma may be effectively targeted using a novel MDSC-based cell therapy approach.

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