hsa_circ_0003738 Inhibits the Suppressive Function of Tregs by Targeting miR-562/IL-17A and miR-490-5p/IFN-γ Signaling Pathway
hsa_circ_0003738 Inhibits the Suppressive Function of Tregs by Targeting miR-562/IL-17A and miR-490-5p/IFN-γ Signaling Pathway
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hsa_circ_0003738 通过靶向 miR-562/IL-17A 和 miR-490-5p/IFN-γ 信号通路抑制 Tregs 的抑制功能
DOI：
10.1016/j.omtn.2020.08.001
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Gang Wang
中科院分区：
文献类型：
--
作者：
Luting Yang;Chen Zhang;Xiaocui Bai;Chunying Xiao;Erle Dang;Gang Wang
调节性T细胞（Treg）抑制功能的功能障碍与银屑病的发病机制有关。越来越多的证据表明环状RNA（circular RNA，circRNA）在调节细胞增殖、凋亡等多种生物学过程中的重要性，但关于circRNA在银屑病皮损抑制中的作用及其机制尚不清楚。在这里，通过使用circRNA微阵列分析，我们发现了四个上调和四个下调的circRNA在银屑病皮损。定量实时PCR进一步证实了银屑病性银屑病中circ_0003738的显著增加。更重要的是，慢病毒敲低银屑病患者T细胞中的circ_0003738可以通过抑制促炎细胞因子白细胞介素-17A（IL-17 A）和干扰素（IFN）-γ的分泌来恢复其抑制功能。此外，我们发现circ_0003738可以与miR-562结合，解除对靶基因IL-17 RA（IL-17 receptor A）的抑制，从而促进银屑病T细胞中的IL-17 A信号传导。同时，circ_0003738还充当miR-490- 5 p的海绵，并减轻了对靶基因IFNGR 2的抑制，IFNGR 2促进了银屑病T细胞中的IFN-γ信号传导。我们的研究表明，上调的circ_0003738通过miR-562/IL 17 RA和miR-490- 5 p/IFNGR 2（IFN-γ受体2）轴降低了银屑病Treg的抑制功能，这表明circRNA参与了功能失调的Treg的发病机制。这些发现将为银屑病的治疗提供新的治疗靶点。
Dysfunction in the suppressive function of regulatory T cells (Tregs) has been related to the pathogenesis of psoriasis. Accumulating evidence has demonstrated the importance of circular RNAs (circRNAs) in regulating various biological process, such as cell proliferation, apoptosis, etc. However, the role of circRNAs in modulating the suppressive functions of psoriatic Tregs and the underlying mechanisms have not been investigated. Here, by using circRNA microarray analysis, we discovered four upregulated and four downregulated circRNAs in psoriatic Tregs. Quantitative real-time PCR further confirmed a significant increase of circ_0003738 in psoriatic Tregs. Importantly, knockdown of circ_0003738 by lentivirus in psoriatic Tregs could restore their suppressive functions via inhibiting the secretion of proinflammatory cytokines interleukin-17A (IL-17A) and interferon (IFN)-γ. Moreover, we found that circ_0003738 could bind to miR-562 to release the inhibition of target gene IL-17RA (IL-17 receptor A), thus promoting IL-17A signaling in psoriatic Tregs. In parallel, circ_0003738 acted also as a sponge for miR-490-5p and relieved inhibition for the target gene IFNGR2, which promoted IFN-γ signaling in psoriatic Tregs. Our study demonstrated that upregulated circ_0003738 decreased the suppressive function of psoriatic Tregs via the miR-562/IL17RA and miR-490-5p/IFNGR2 (IFN-γ receptor 2) axis, which indicated the involvement of circRNAs in the pathogenesis of dysfunctional Tregs. These findings will provide new therapeutic targets for the treatment of psoriasis.
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DOI：
10.4049/jimmunol.0803721
发表时间：
2009-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Goodman WA;Levine AD;Massari JV;Sugiyama H;McCormick TS;Cooper KD
通讯作者：
Cooper KD
影响因子：
7.3
作者：
Hippen KL;Loschi M;Nicholls J;MacDonald KPA;Blazar BR
通讯作者：
Blazar BR
影响因子：
5
作者：
Meng-yuan Zhou;Jin-Ming Yang;X. Xiong
通讯作者：
Meng-yuan Zhou;Jin-Ming Yang;X. Xiong
影响因子：
16.6
作者：
Kimura K;Hohjoh H;Fukuoka M;Sato W;Oki S;Tomi C;Yamaguchi H;Kondo T;Takahashi R;Yamamura T
通讯作者：
Yamamura T
影响因子：
--
作者：
Qiao, Meng;Ding, Jian;Sun, Qing
通讯作者：
Sun, Qing