LncRNA-AP4B1/SNRPA复合体通过调控PTPN22转录影响银屑病FoxP3+调节性T细胞的稳定性及机制研究

银屑病FoxP3+调节性T细胞（FoxP3+Treg）不稳定，可转变为效应T细胞，导致的免疫失衡参与银屑病发展，但其稳定性机制尚不明确。我们通过银屑病皮损组织LncRNAs/邻近mRNAs联合差异分析发现，影响TCR信号强度-Treg稳定性轴的蛋白酪氨酸磷酸酶非受体型22（PTPN22）和LncRNA-AP4B1在皮损FoxP3+Treg中显著增高，且提示PTPN22可受后者调控。另前期研究提示，催化mRNA剪切的小核核糖核蛋白A（SNRPA）与LncRNA-AP4B1形成复合体协同作用。结合文献及前期基础，提出LncRNA-AP4B1/SNRPA复合体调控PTPN22转录，影响TCR信号强度，进而调控FoxP3+Treg稳定性的机制。拟在Treg、细胞系和动物模型水平，阐明该机制，为完善Treg调控网络奠定基础，为精准调控银屑病FoxP3+Treg稳定性提供靶点，为银屑病治疗提供新策略。

Dysregulation of the stability is one of the main characteristics of FoxP3+ regulatory T cells (FoxP3+Tregs) in psoriasis. Psoriatic FoxP3+Tregs are prone to convert into effector T cells. It causes an immune imbalance that plays a pivotal role in the chronic course of psoriasis. However, the mechanism of FoxP3+Treg's stability is not entirely clear. By combination analysis of psoriatic tissue differential LncRNAs and adjacent mRNAs, we find that both LncRNA-AP4B1 and PTPN22 (protein tyrosine phosphatase non-receptor type 22) are up-regulated in psoriatic FoxP3+Tregs. PTPN22 is key to regulating TCR (T cell receptor) signaling intensity and Treg stability. Moreover, PTPN22 is suggested by the combination analysis to be regulated by LncRNA-AP4B1. Furthermore, our preliminary data suggest SNRPA (small nuclear ribonucleoprotein A) form a complex with LncRNA-AP4B1 to play synergy roles. Based on literatures and our previous studies, we propose that LncRNA-AP4B1/SNRPA complex governs the stability of psoriatic FoxP3+Tregs through influencing TCR signaling intensity by regulating PTPN22 transcription. This new mechanism will be elucidated at the levels of psoriatic Tregs, cell lines, and animal models. These studies will lay the foundation for the regulatory mechanisms of FoxP3+Tregs differentiation and function, provide intervention targets for regulating the stability of psoriatic FoxP3+Tregs, and provide new strategies for the treatment and management of chronic course of psoriasis.