Probiotics can be an effective treatment for atopic dermatitis (AD), while their mechanism of action is still unclear. Here, we induced AD in mice with 2,4-dinitrochlorobenzene and administrated YK4, a probiotic mixture consisting of Lactobacillus acidophilus CBT LA1, L. plantarum CBT LP3, Bifidobacterium breve CBT BR3, and B. lactis CBT BL3. Then, we have validated the underlying mechanism for the alleviation of AD by YK4 from the intestinal and systematic immunological perspectives. Administration of YK4 in AD mice alleviated the symptoms of AD by suppressing the expression of skin thymic stromal lymphopoietin and serum immunoglobulin E eliciting excessive T-helper (Th) 2 cell-mediated responses. YK4 inhibited Th2 cell population through induce the proportion of Th1 cells in spleen and Treg cells in Peyer's patches and mesenteric lymph node (mLN). CD103+ dendritic cells (DCs) in mLN and the spleen were significantly increased in AD mice administered with YK4 when compared to AD mice. Furthermore, galectin-9 was significantly increased in the gut of AD mice administered with YK4. In vitro experiments were performed using bone marrow-derived DCs (BMDC) and CD4+ T cells to confirm the immune mechanisms of YK4 and galectin-9. The expression of CD44, a receptor of galectin-9, together with programmed death-ligand 1 was significantly upregulated in BMDCs following treatment with YK4. IL-10 and IL-12 were upregulated when BMDCs were treated with YK4. Cytokines together with co-receptors from DCs play a major role in the differentiation and activation of CD4+ T cells. Proliferation of Tregs and Th1 cell activation were enhanced when CD4+T cells were co-cultured with YK4-treated BMDCs. Galectin-9 appeared to contribute at least partially to the proliferation of Tregs. The results further suggested that DCs treated with YK4 induced the differentiation of naïve T cells toward Th1 and Tregs. At the same time, YK4 alleviated AD symptoms by inhibiting Th2 response. Thus, the present study suggested a potential role of YK4 as an effective immunomodulatory agent in AD patients.

中文翻译：

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膳食益生菌混合物诱导的半乳凝素9调节免疫平衡，减少小鼠特应性皮炎症状。

益生菌可以有效治疗特应性皮炎（AD），但其作用机理尚不清楚。在这里，我们用2,4-二硝基氯苯诱导小鼠AD，并施用YK4，益生菌混合物包括嗜酸乳杆菌CBT LA1，植物乳杆菌CBT LP3，短双歧杆菌CBT BR3和乳酸杆菌CBT BL3。然后，我们从肠道和系统免疫学角度验证了YK4减轻AD的潜在机制。在AD小鼠中施用YK4可通过抑制皮肤胸腺基质淋巴细胞生成素和血清免疫球蛋白E的表达，从而引起过多的T-helper（Th）2细胞介导的反应来缓解AD症状。YK4通过诱导脾脏中的Th1细胞和淋巴结中的Treg细胞的比例来抑制Th2细胞群 斑块和肠系膜淋巴结（mLN）。与AD小鼠相比，使用YK4的AD小鼠的mLN和脾脏中的CD103 +树突状细胞（DC）显着增加。此外，在施用YK4的AD小鼠的肠道中，galectin-9显着增加。使用骨髓来源的DC（BMDC）和CD4 + T细胞进行了体外实验，以确认YK4和Galectin-9的免疫机制。在用YK4治疗后，BMDC中CD44（一种半乳糖凝集素9受体）的表达与编程的死亡配体1一起显着上调。当用YK4处理BMDC时，IL-10和IL-12上调。细胞因子与DC的共受体一起在CD4 + T细胞的分化和激活中起主要作用。当CD4 + T细胞与YK4处理的BMDC共培养时，Tregs的增殖和Th1细胞的活化得到增强。Galectin-9似乎至少部分有助于Tregs的增殖。结果进一步表明，用YK4处理的DC诱导幼稚T细胞向Th1和Tregs分化。同时，YK4通过抑制Th2反应缓解了AD症状。因此，本研究提示YK4作为AD患者中有效的免疫调节剂的潜在作用。