PSORI-CM02 alleviates IMQ-induced mouse dermatitis via differentially regulating pro- and anti-inflammatory cytokines targeting of Th2 specific transcript factor GATA3
PSORI-CM02 alleviates IMQ-induced mouse dermatitis via differentially regulating pro- and anti-inflammatory cytokines targeting of Th2 specific transcript factor GATA3
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PSORI-CM02 通过差异调节针对 Th2 特异性转录因子 GATA3 的促炎和抗炎细胞因子来减轻 IMQ 诱导的小鼠皮炎
DOI：
10.1016/j.biopha.2018.11.092
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发表时间：
2019
影响因子：
7.5
通讯作者：
Lu Chuan-jian
中科院分区：
文献类型：
--
作者：
Wu Ding-hong;Zhang Miao-miao;Li Ning;Li Xiong;Cai Quan-wei;Yu Wan-lin;Liu Li-ping;Zhu Wei;Lu Chuan-jian
产生IL-17的CD 4 + T细胞和γδT细胞在银屑病（PS）的发病机制中起重要作用。PSORI-CM 02是中国南方治疗PS的代表性草药配方。临床证实能改善PS，无明显副作用。在此，我们试图阐明PSORI-CM 02是否以及如何在IMQ诱导的银屑病样BALB/c小鼠模型中调节T细胞分化和功能。用PSORI-CM 02预处理3天的小鼠显著减轻皮肤炎症，如PASI评分和病理切片中的经典银屑病特征降低。与对照组相比，PSORI-CM 02组皮损中的CD 3和CD 4阳性T细胞也减少。PSORI-CM 02还降低了小鼠皮肤损伤中促炎性IFNγ mRNA和IL-17 A mRNA，而增加了IL-4 mRNA。在皮肤引流淋巴结（DLN）中，PSORI-CM 02可降低γδT细胞的比例，抑制其产生IL-17 A的功能。而PSORI-CM 02对总TCRβ+T细胞和CD 4 + T细胞的比例无影响。但其对DLN中CD 4 + T辅助细胞的分化有调节作用，导致DLN中产生IFNγ的Th 1细胞和产生IL-17 A的Th 17细胞比例下降，而产生IL-4的Th 2细胞比例升高。PSORI-CM 02能促进Th 2特异性转录因子GATA 3的表达，但对T-bet和RORγ无影响。因此，我们初步解释PSORI-CM 02通过促进靶向GATA 3的Th 2细胞应答来损害MQ诱导的银屑病。
The IL-17-producing CD4+ T cell and γδT cells play critical roles in the pathogenesis of psoriasis (PS). PSORI-CM02 is a representative herbal formula for the treatment for PS in South China. It was confirmed to improve PS without obvious side effects in the clinic. Here we sought to clarify whether and how PSORI-CM02 regulates T cell differentiation and functions in IMQ-induced psoriasis-like BALB/c mouse model. Mice pre-treated 3 days with PSORI-CM02 significantly alleviated skin inflammation, as reduced in PASI score and classic psoriatic characteristics in pathological sections. CD3 and CD4 positive T cells were also fewer in the skin lesions of PSORI-CM02 groups, comparing to control group. PSORI-CM02 also decreased pro-inflammatory IFNγ mRNA and IL-17 A mRNA, while increased IL-4 mRNA in mouse skin lesions. In skin draining lymph nodes (DLN), PSORI-CM02 reduced the ratio of γδT cells and inhibited their function of producing IL-17 A. Nevertheless PSORI-CM02 had no effects on the ratio of total TCRβ+T cells and CD4 + T cells. But it regulated CD4 + T helper cells differentiation, and resulted in the decreasing percentage of IFNγ producing Th1 cells and IL-17 A producing Th17 cells, while increasing the ratio of IL-4 producing Th2 cells in DLN. Further data showed that PSORI-CM02 promote expression of Th2 specific transcript factor GATA3, but had no effects on T-bet and RORγ. Thus, we tentatively interpret that PSORI-CM02 impairs IMQ-induced psoriasis by promoting Th2 cell response targeting of GATA3.