Department of Clinical Pathology, Suwon Science College, Hwaseong 18323, South Korea.
Department of Biological science, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
Int Immunopharmacol. 2020 Sep;86:106553. doi: 10.1016/j.intimp.2020.106553. Epub 2020 Jun 17.
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 CD4CD25FoxP3 regulatory T (Treg) cells and decreased the proportions of CD4IFN-γ Th1 cells and CD4IL-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.
虽然他克莫司（FK-506）已被证明是一种有效的银屑病单药治疗方法，但它并不总是有效。目前，联合治疗经常用于治疗银屑病，因为临床试验表明它可能提供附加或协同益处，并降低不良反应的风险。髓源性抑制细胞（MDSCs）在自身免疫性疾病中具有强大的免疫调节和抗炎特性。我们之前报道过 MDSCs 在咪喹莫特（IMQ）诱导的银屑病小鼠模型中具有保护作用。本研究旨在探讨 MDSC 加 FK-506 对咪喹莫特诱导的银屑病小鼠模型的全身免疫调节和治疗效果，并探讨其涉及的免疫调节机制。我们发现，MDSC 加 FK-506 全身治疗在小鼠模型中具有显著的抗银屑病作用，可降低血清和皮肤中促炎细胞因子 Th1 细胞因子（TNF-α 和 IFN-γ）和 Th17 细胞因子（IL-17A 和 IL-23）的水平。然而，单独使用 MDSC 或 FK-506 治疗几乎没有影响。此外，MDSC 加 FK-506 的抗银屑病作用与炎症浸润、表皮增生和角化过度的组织病理学减少有关。此外，这种联合治疗还可减轻 IMQ 诱导的脾肿大，并增加脾中 CD4CD25FoxP3 调节性 T（Treg）细胞的比例，降低 CD4IFN-γ Th1 细胞和 CD4IL-17 Th17 细胞的比例。总之，我们的结果表明，MDSC 和 FK-506 的全身联合治疗在我们的 IMQ 诱导的银屑病模型中比单独使用任何一种药物都具有更好的治疗效果，并表明这种联合治疗可能对管理银屑病等自身免疫性皮肤病有用。
