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髓源性抑制细胞对咪喹莫特诱导的小鼠皮肤炎症的抗银屑病作用。

Anti-psoriatic effect of myeloid-derived suppressor cells on imiquimod-induced skin inflammation in mice.

机构信息

College of Medicine, Dongguk University, Goyang, Korea.

College of Pharmacy, Kyung Hee University, Seoul, Korea.

出版信息

Scand J Immunol. 2019 Mar;89(3):e12742. doi: 10.1111/sji.12742. Epub 2019 Jan 15.

DOI:10.1111/sji.12742
PMID:30548969
Abstract

Myeloid-derived suppressor cells (MDSCs) play an important role in controlling the immune response against cancer and in suppression of autoimmunity and allergic inflammation. However, the beneficial effects of MDSCs on the experimental mouse model of psoriasis have not been reported. Therefore, we investigated the anti-psoriatic effect of MDSCs on IMQ-induced skin inflammation in mice and explored the mechanisms involved. Our results showed that administration of MDSCs (1 × 10 or 2 × 10  cells) suppressed the development of IMQ-induced skin inflammation in mice as exemplified by a significant reduction in clinical severity scores and was associated with a reduction of histopathological changes, including inflammatory infiltration, epidermal hyperplasia and hyperkeratosis. The immunosuppressive effect of MDSCs (1 × 10 or 2 × 10  cells) corresponded to the production of Th1 cytokines (TNF-α, IFN-γ) and Th17 cytokines (IL-17A and IL-23) in the serum and dorsal skin. Administration of MDSCs (1 × 10 or 2 × 10  cells) also inhibited splenomegaly. Moreover, an increased percentage of CD4 CD25 FoxP3 regulatory T (Treg) cells and decreased percentage of Th1 and Th17 cells were found in mice treated with MDSCs. Taken together, these results imply that MDSCs have immunomodulatory and immunosuppressive effects on disease progression in a murine model of psoriasis and that MDSCs could be used in preventive or therapeutic strategies for the management of autoimmune inflammatory skin disorders, such as psoriasis.

摘要

髓系来源的抑制细胞(MDSCs)在控制抗肿瘤免疫反应以及抑制自身免疫和过敏炎症方面发挥着重要作用。然而,MDSCs 对银屑病实验性小鼠模型的有益作用尚未见报道。因此,我们研究了 MDSCs 对咪喹莫特(IMQ)诱导的小鼠皮肤炎症的抗银屑病作用,并探讨了其相关机制。我们的结果表明,MDSCs(1×10 或 2×10 个细胞)的给药抑制了 IMQ 诱导的小鼠皮肤炎症的发展,表现为临床严重程度评分显著降低,并伴有组织病理学变化的减少,包括炎症浸润、表皮增生和角化过度。MDSCs(1×10 或 2×10 个细胞)的免疫抑制作用与血清和背部皮肤中 Th1 细胞因子(TNF-α、IFN-γ)和 Th17 细胞因子(IL-17A 和 IL-23)的产生相对应。MDSCs(1×10 或 2×10 个细胞)的给药还抑制了脾肿大。此外,在接受 MDSCs 治疗的小鼠中,发现 CD4 CD25 FoxP3 调节性 T(Treg)细胞的百分比增加,Th1 和 Th17 细胞的百分比降低。综上所述,这些结果表明 MDSCs 对银屑病小鼠模型的疾病进展具有免疫调节和免疫抑制作用,并且 MDSCs 可用于预防或治疗自身免疫性炎症性皮肤疾病,如银屑病的策略。

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