Expansion of CD11bLy-6C myeloid-derived suppressor cells (MDSCs) driven by galectin-9 attenuates CVB3-induced myocarditis.

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 CD11bLy-6C myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11bLy-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 CD11bLy-6C MDSCs to ameliorate CVB3-induced myocarditis.