Methods: ASCs were injected intravenously in wild-type (WT) and IDO-KO asthmatic mice. PGE2 inhibitor and TGF-β neutralizing antibodies were injected intraperitoneally on four consecutive days at the approximate time of ASCs injection. We investigated the immunomodulatory effects of ASCs between WT and IDO-KO mice, WT mice treated with and without PGE2 inhibitor, and WT mice treated with and without anti-TGF-β antibodies respectively.
Results: In WT and IDO-KO asthmatic mice, ASCs significantly reduced airway hyperresponsiveness, total inflammatory cells and eosinophils in the bronchoalveolar lavage fluid (BALF), eosinophilic inflammation, goblet cell hyperplasia, and serum total and allergen-specific IgE and IgG1. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the BALF and lung draining lymph nodes (LLNs). Furthermore, ASCs engraftment caused significant increases the regulatory T cells (Tregs) and IL-10+ T cells populations in LLNs. However, when treating mice with PGE2 inhibitor and TGF-β neutralizing antibodies, blocking PGE2 and TGF-β, but not IDO-KO mice, eliminated the immunosuppressive effect of ASCs in allergic airway inflammation.
Conclusion: ASCs themselves are capable of secreting PGE2 and TGF-β, which may play a role in inducing Tregs expansion. Furthermore, PGE2 inhibitor and TGF-β neutralizing antibodies eliminated the beneficial effect of ASCs treatment in asthmatic mice, suggesting that PGE2 and TGF-β are the major soluble factors in suppressing the allergic airway inflammation.