从Fabp4/5介导的外源性脂肪酸代谢研究养血解毒方对银屑病皮损组织驻留记忆T细胞存活和功能的调节作用

银屑病的长病程和复发机制与病理性的免疫记忆相关，组织驻留记忆性T细胞(TRM)是参与银屑病皮损处病理性免疫记忆的主要细胞。Fabp4/5介导的外源性脂肪酸代谢是TRM特有的并得以在皮肤组织中长期存活所必需的供能方式。血燥证是银屑病慢性病程的主要证候，养血解毒方有良好的临床疗效。前期研究证实该方可减轻/延缓银屑病复发，减少皮损TRM的比例，并抑制Fabp4/5的表达。以此为线索，本项目通过临床皮损检测及动物实验，进一步明确养血解毒方对TRM存活、功能、Fabp4/5表达、脂肪酸代谢的调节作用，并探索其作用环节。同时通过体外TRM实验结合ATAC-Seq检测，观察养血解毒方对“差异转录因子→Fabp4/5依赖的外源性脂肪酸代谢→TRM活性和功能”的干预作用，阐明养血解毒方的作用靶点。通过临床、动物、细胞多层次的研究，为养血解毒方治疗银屑病及延缓/减轻复发的临床应用提供生物学证据。

The maintenance and recurrence of psoriatic lesion is driven by inappropriate and chronic activation of pathogenic tissue resident memory T cells (TRM) which is the key player contributing to pathologic immune memory. The uniqueness of TRM in their dependence on lipid metabolism of exogenous FFAs mediated by Fabp4/5 makes it a previously unappreciated weakness and one that could be exploited therapeutically. The blood-dryness is the main syndrome of chronic course of patients with psoriasis. Clinically, nourishing blood and detoxification is the principle and YangXueJieDu prescription is an effective treatment. Our preliminary data demonstrated that this decoction markedly inhibit TRM survival in IMQ-induced psoriatic lesion and suppress the expression of Fabp4/5. Along this clue, we try to better chase our understanding of this decoction via investigating the regulatory effect of this decoction on the function and survival of TRM, Fabp4/5 expression as well as fatty acid metabolism in clinical psoriatic involved skin samples and animal experiments. Moreover, we employ in vitro TRM model and perform ATAC-Seq, attempting to uncover the intervention effect and mechanisms of this decoction on differential transcription factor-mediated signaling pathways. Via clinical detection, animal experiments in vivo and TRM research in vitro, we hope to uncover the mechanisms of this decoction on treating psoriasis and provide the theoretical basis for clinical application.