Expansion of CD11b+Ly-6C+ myeloid-derived suppressor cells (MDSCs) driven by galectin-9 attenuates CVB3-induced myocarditis

Abstract Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b + Ly-6C + myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b + Ly-6C + MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C + MDSCs, but not Ly6G + cells, expressed Arg-1 and NOS2, and suppressed CD4 + T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l -arginine. Furthermore, Ly6C + MDSCs co-expressed higher levels of F4/80, Tim-3, and IL-4Rα, and had the plasticity to up-regulate NOS2 or Arg-1 in response to IFN-γ or IL-4 treatment. The present results indicate that galectin-9 expands CD11b + Ly-6C + MDSCs to ameliorate CVB3-induced myocarditis.