LncRNA-LIPE 01/04剪切体通过时相调节CXCL17调控银屑病BDCA1-CD11c+ 髓样树突状细胞的功能及机制研究

Over-activation of effective T cells in the lesions is vital to the stubborn development of psoriasis. Psoriatic BDCA1-CD11c+ mDCs（Pso-mDCs）play an important role in the over-activation of effective T cells. However, the regulatory mechanism of Pso-mDCs is unclear. Our previous study of LncRNAs and adjacent mRNAs joint variance analysis shows that there is a consistent change trend among LncRNA-LIPE 01/04 transcripts, chemokine CXCL17, and Pso-mDCs when normal skins change into psoriatic lesion, and into recovery skin. Our preliminary study suggests that CXCL17 is likely the target of LncRNA-LIPE. In addition, CXCL17 can promote the IL-23 secretion of Pso-mDCs. Based on the published studies and our preliminary experimental results, we propose that lncRNA-LIPE 01/04 transcripts regulate psoriatic BDCA1-CD11c+ mDCs through dynamic adjustment of CXCL17. We plan to clear the regulatory mechanism of Pso-mDCs on cells and animal modes levels. This study will be helpful to specifically shut-down these proinflammatory Pso-mDCs. It will provide strategic basis to explore novel alternative therapeutic target. Our study will establish new foundation to the pathogenesis of psoriasis.

皮损炎症微环境中T细胞过度活化是银屑病顽固发展的主要环节，银屑病树突状细胞亚群 BDCA1-CD11c+mDCs（Pso-mDCs）在T细胞过度活化中起重要作用，但其本身调控机制尚不明确。我们通过LncRNAs/邻近mRNAs联合差异分析等发现，LncRNA-LIPE 01/04剪切体、新型趋化因子样蛋白CXCL17及Pso-mDCs在银屑病皮损发展、转归中变化显著且一致。且我们前期研究提示CXCL17是LncRNA-LIPE调控的靶基因，可促进Pso-mDCs分泌IL-23。结合文献和前期基础，我们提出LncRNA-LIPE 01和04剪切体分別在发展期、恢复期两个时相调节CXCL17转录，进而调控银屑病Pso-mDCs功能的机制。拟在细胞、动物模型等水平上阐明Pso-mDCs调控的分子机制，为精准“关闭”该促炎亚群、研发治疗新靶点提供策略依据，为深入阐明银屑病发病机制奠定新的理论基础。

皮损炎症微环境中T细胞过度活化是银屑病顽固发展的主要环节，银屑病树突状细胞亚群BDCA1-CD11c+mDCs（Pso-mDCs）在T细胞过度活化中起重要作用，但其本身调控机制尚不明确。我们通过LncRNAs/邻近mRNAs联合差异分析等发现，LncRNA-LIPE剪切体、新型趋化因子样蛋白CXCL17及Pso-mDCs在银屑病皮损发展、转归中变化显著且一致。且我们前期研究提示CXCL17是LncRNA-LIPE调控的靶基因，可促进Pso-mDCs分泌IL-23。结合文献和前期基础，我们在细胞、动物模型等水平上证实了LncRNA-LIPE-AS1分別在不同时相调节CXCL17转录，CXCL17进而通过对BCL2L2的调控，实现调控银屑病Pso-mDCs功能的分子机制。研究为精准“关闭”该促炎亚群、研发治疗新靶点提供策略依据，为深入阐明银屑病发病机制奠定新的理论基础。