Although
tacrolimus (FK-506) has been shown to be an effective monotherapy for
psoriasis, it does not always work well. Currently, combination
therapy is frequently used to manage
psoriasis because clinical trials have shown it may provide additive or synergistic benefits and reduce risks of adverse effects. Myeloid-derived suppressor cells (MDSCs) have potent immunomodulatory and anti-inflammatory properties in
autoimmune diseases. We previously reported that MDSCs had protective effects in a murine model of
imiquimod (IMQ)-induced
psoriasis. The present study was undertaken to investigate the systemic immunomodulatory and therapeutic efficacy effects of MDSC plus
FK-506 in an IMQ-induced mouse model of
psoriasis and to investigate the immunomodulatory mechanisms involved. Systemic MDSC plus
FK-506 therapy was found to have a significant anti-psoriatic effect in the murine model, to reduce levels of pro-inflammatory
cytokines Th1
cytokines (TNF-α and IFN-γ) and Th17
cytokines (IL-17A and IL-23) in serum and skin. However, treatment with MDSCs or
FK-506 alone had little impact. Furthermore, the anti-psoriatic effects of MDSC plus
FK-506 were associated with histopathological reductions in inflammatory infiltration, epidermal
hyperplasia, and hyperkeratosis. In addition, this combined treatment also attenuated IMQ-induced
splenomegaly, and increased the proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells and decreased the proportions of CD4+IFN-γ+ Th1 cells and CD4+IL-17+ Th17 cells in spleen. Taken together, our results show systemic combination
therapy with MDSCs and
FK-506 had a better
therapeutic effect in our IMQ-induced
psoriasis model than either agent alone, and suggest that this combinatorial
therapy might be useful for the management of autoimmune
skin diseases like
psoriasis.