Lee Yun Sang, Sah Shyam Kishor, Lee Ji Hyun, Seo Kwang-Won, Kang Kyung-Sun, Kim Tae-Yoon
Department of Dermatology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040, South Korea.
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
Biochem Biophys Rep. 2016 Oct 8;9:281-288. doi: 10.1016/j.bbrep.2016.10.002. eCollection 2017 Mar.
Mesenchymal stem cells (MSCs) inhibit the proliferation or activation of lymphocytes, and their inhibitory effects do not require human leukocyte antigen (HLA)-matching because MSCs express low levels of HLA molecules. Therefore, MSCs may be able to regulate immune responses. In this study, we determined whether MSCs could inhibit psoriasis-like skin inflammation in mice. After induction of psoriasis-like skin inflammation using intradermal injection of IL-23 or topical application of imiquimod with or without treatment with MSC, mouse skins were collected, and H&E staining and real-time PCR were performed. IL-23-induced skin inflammation was inhibited when MSCs were injected on day -1 and day 7. The expression of proinflammatory cytokines such as IL-6, IL-17, and TNF-α was inhibited by MSC injection, and the expression of chemokines such as CCL17, CCL20, and CCL27 was also decreased in mouse skin. We also determined whether MSCs could not only prevent but also treat psoriasis-like skin inflammation in mice. Furthermore, in vitro experiments also showed anti-inflammatory effects of MSCs. Dendritic cells which are co-cultured with MSCs suppressed CD4+ T cell activation and differentiation, which are important for the pathogenesis of psoriasis. These results suggest that MSCs could be useful for treating psoriasis.
间充质干细胞(MSCs)可抑制淋巴细胞的增殖或活化,且由于其HLA分子表达水平较低,其抑制作用无需人白细胞抗原(HLA)匹配。因此,MSCs可能能够调节免疫反应。在本研究中,我们确定了MSCs是否能够抑制小鼠的银屑病样皮肤炎症。使用皮内注射IL-23或局部应用咪喹莫特诱导银屑病样皮肤炎症,无论是否用MSCs治疗,之后收集小鼠皮肤,并进行苏木精-伊红(H&E)染色和实时聚合酶链反应(PCR)。在第-1天和第7天注射MSCs时,IL-23诱导的皮肤炎症受到抑制。注射MSCs可抑制促炎细胞因子如IL-6、IL-17和TNF-α的表达,小鼠皮肤中趋化因子如CCL17、CCL20和CCL27的表达也降低。我们还确定了MSCs是否不仅能预防而且能治疗小鼠的银屑病样皮肤炎症。此外,体外实验也显示了MSCs的抗炎作用。与MSCs共培养的树突状细胞抑制了CD4+T细胞的活化和分化,而这对银屑病的发病机制很重要。这些结果表明,MSCs可能对治疗银屑病有用。