Kim Han Wool, Hong Rira, Choi Eun Young, Yu KeeSun, Kim Narae, Hyeon Jin Yi, Cho Kwang Keun, Choi In Soon, Yun Cheol-Heui
Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
Department of Biological Science, College of Medical and Life Sciences, Silla University, Busan, South Korea.
Front Microbiol. 2018 Oct 15;9:2414. doi: 10.3389/fmicb.2018.02414. eCollection 2018.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex etiology involving the immune response. Recent studies have demonstrated the role of certain probiotics in the treatment and prevention of AD. However, the mechanism by which these probiotics regulate the immune system remains unclear. In this study, we examined the immunomodulatory capacity of Duolac ATP, a mixed formulation of probiotics, both and . Results showed that the expression of programmed death-ligand 1(PD-L1) was significantly upregulated on bone marrow-derived dendritic cells (BMDCs) treated with Duolac ATP. Furthermore, the anti-inflammatory cytokines IL-10 and TGF-beta were both upregulated when BMDCs were treated with Duolac ATP. The percentage of proliferated regulatory T cells (Tregs) was enhanced when CD4 T cells were co-cultured with Duolac ATP-treated BMDCs on plates coated with anti-CD3/CD28 antibodies. Intriguingly, IL-10 secretion from CD4 T cells was also observed. The AD symptoms, histologic scores, and serum IgE levels in AD mice were significantly decreased after oral treatment with Duolac ATP. Moreover, the Th1-mediated response in AD-induced mice treated with oral Duolac ATP showed upregulation of IL-2 and IFN-gamma as well as of downstream signaling molecules T-bet, STAT-1, and STAT-4. Conversely, Duolac ATP suppressed Th2 and Th17 responses in AD-like mice, as evidenced by the downregulation of GATA-3, C-maf, IL-4, IL-5, and IL-17. Additionally, Duolac ATP increased the number of Tregs found at Peyer's patches (PP) in treated AD mice. These results suggest that Duolac ATP modulates DCs to initiate both Th1 and Treg responses in AD mice. Thus, Duolac ATP represents a potential preventative agent against AD and could serve as an effective immunomodulator in AD patients.
特应性皮炎（AD）是一种慢性炎症性皮肤病，病因复杂，涉及免疫反应。最近的研究表明某些益生菌在AD的治疗和预防中发挥作用。然而，这些益生菌调节免疫系统的机制仍不清楚。在本研究中，我们检测了益生菌混合制剂多乐可ATP在体内和体外的免疫调节能力。结果显示，用多乐可ATP处理的骨髓来源树突状细胞（BMDCs）上程序性死亡配体1（PD-L1）的表达显著上调。此外，当BMDCs用多乐可ATP处理时，抗炎细胞因子IL-10和转化生长因子-β均上调。当CD4 T细胞与用多乐可ATP处理的BMDCs在包被有抗CD3/CD28抗体的平板上共培养时，增殖的调节性T细胞（Tregs）百分比增加。有趣的是，还观察到CD4 T细胞分泌IL-10。口服多乐可ATP后，AD小鼠的AD症状、组织学评分和血清IgE水平显著降低。此外，口服多乐可ATP处理的AD诱导小鼠中，Th1介导的反应显示IL-2、干扰素-γ以及下游信号分子T-bet、信号转导和转录激活因子1（STAT-1）和信号转导和转录激活因子4（STAT-4）上调。相反，多乐可ATP抑制了类AD小鼠中的Th2和Th17反应，GATA-3、C-maf、IL-4、IL-5和IL-17的下调证明了这一点。此外，多乐可ATP增加了治疗的AD小鼠派尔集合淋巴结（PP）中Tregs的数量。这些结果表明，多乐可ATP调节DCs以启动AD小鼠中的Th1和Treg反应。因此，多乐可ATP是一种潜在的AD预防剂，可作为AD患者有效的免疫调节剂。
