Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway.
Ebosin Ameliorates Psoriasis-Like Inflammation of Mice via miR-155 Targeting tnfaip3 on IL-17 Pathway.
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DOI：
10.3389/fimmu.2021.662362
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发表时间：
2021
影响因子：
7.3
通讯作者：
Bai L
中科院分区：
文献类型：
--
作者：
Guo W;Xu F;Zhuang Z;Liu Z;Xie J;Bai L
银屑病是一种反复发作的自身免疫性皮肤病，角质形成细胞和免疫细胞的调节异常。目前还没有普遍接受的单一治疗银屑病的方法，迫切需要建立一种共同的治疗方案来控制其症状和体征。在这里，我们发现了从链霉菌中分离到的一种新的胞外多糖--埃博菌素。139本实验室通过IKK/NF-Kapab途径，不仅可以减轻脂多糖诱导的角质形成细胞的炎症反应，而且可以减轻咪喹莫特(Imiquimod，ImQ)诱导的银屑病小鼠皮肤病变，减少炎症因子的表达。除抑制表皮分化相关蛋白的表达外，依博斯汀还能显著提高银屑病小鼠外周血中CD4+Foxp3+CD25+Tregs的百分率，降低CD4+IL17A+Th17细胞的百分率。此外，我们在体内证明了依博斯汀通过A20(由TNFAIP3编码)显著抑制了IL-17信号通路。由于荧光素酶报告实验证实了TNFAIP3与miR-155的直接结合，以及依博菌素在体内外对miR-155水平的抑制作用，我们的研究首次表明，依博菌素通过miR-155-TNFAIP3-IL-17轴和T细胞分化在银屑病样模型中减轻炎症。因此，我们得出结论，依博菌素可以作为治疗银屑病的有前途的候选药物。
Psoriasis is a recurrent autoimmune skin disease with aberrant regulation of keratinocytes and immunocytes. There is no universally accepted single treatment available for psoriasis, and the establishment of a common treatment option to control its signs and symptoms is urgently needed. Here, we found Ebosin, a novel exopolysaccharide isolated from Streptomyces sp. 139 by our lab, not only could ameliorate inflammation in LPS-induced keratinocytes through IKK/NF-kapaB pathway, but also attenuate psoriatic skin lesions and reduce inflammatory factors expression in imiquimod (IMQ)-mediated psoriatic mice. Except for inhibiting the expression of epidermal differentiation related proteins, Ebosin significantly increased the percentage of CD4+Foxp3+CD25+ Tregs and decreased CD4+IL17A+ Th17 cells in psoriatic mice. Furthermore, we demonstrate that Ebosin significantly suppressed the IL-17 signaling pathway via A20 (encoded by tnfaip3) in vivo. As the direct binding of tnfaip3 to miR-155 has been demonstrated by luciferase reporter assay, and Ebosin has been demonstrated to inhibit miR-155 level in vitro and in vivo, our study first indicates that Ebosin reduces inflammation through the miR-155-tnfaip3-IL-17 axis and T cell differentiation in a psoriasis-like model. Thus, we conclude that Ebosin can act as a promising therapeutic candidate for the treatment of psoriasis.
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