Mesenchymal stem cells overexpressing interleukin-10 prevented allergic airway inflammation

Abstract

Abstract Backgrounds: Allergic airway inflammation is widely distributed worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties. Methods Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs) were engineered to overexpress IL-10 by lentivirus transfection (designated as IL-10-MSCs). The MSCs and IL-10-MSCs were administrated intravenously to the mice induced as allergic inflammation using ovalbumin (OVA), and the features of allergic inflammation, including inflammatory cell infiltration, Th cells in lung and T helper 2 cells (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the level of Th2 cells and the expression of corresponding type 2 cytokines were studied. RNA-sequence was employed to further probe the potential effects of MSCs and IL-10-MSCs on CD4+ T cells. Results Stable IL-10-MSCs were established and characterized as high expression of IL-10. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in lung tissue of mice with allergic airway inflammation. Inflammatory cells and cytokine levels in BALF were also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed stronger capacity to inhibit the levels of Th2 after cocultured with CD4+ T cells from patients of AR. Furthermore, we found the lower levels of IL-5 and IL-13 for IL-10-MSCs treated CD4+ T cells, and the blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We further reported the mRNA profiles for CD4+ T cells treated with IL-10-MSCs and MSCs, and in which IL-10 exerts an important role. Conclusion We identified that IL-10-MSCs showed good effects in the treatment of allergic airway inflammation, providing solid support for genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.