基于抑制PI3K/AKT/mTOR信号通路调控CD4+Foxp3+Treg探讨银屑灵优化方治疗银屑病的作用机制

Psoriasis is a T cell-mediated immune disease that affects 2-3% of the population. PSORI-CM02 formula is the experimental formula of Professor Guowei Xuan, National Medical Master, for the therapy of psoriasis with exact clinical efficacy. It is urgently needed to clarify the mechanism of action of PSORI-CM02 formula. Inhibition of PI3K/AKT/mTOR signaling pathway can induce Foxp3 expression and up-regulate the frequency of Treg. Treg is an immunomodulatory T-cell subtype that plays an important role in the treatment of psoriasis. Our previous study found that PSORI-CM02 formula can effectively alleviate the skin lesions in psoriatic mice, inhibit the expression of p-mTOR and p-AKT protein and up-regulate the frequency of CD4+Foxp3+ Treg cells. Therefore, we make the scientific hypothesis that "PSORI-CM02 formula can inhibite the PI3K/AKT/mTOR signaling pathway to increase the frequency of CD4+ Foxp3+ Treg in the treatment of psoriasis". In this study, Naïve CD4 + T cells and Tregs in psoriatic patient and psoriatic mice will be sorted to investigate the effect of PSORI-CM02 formula mechanism of PI3K/AKT/mTOR signaling pathway and Treg cell differentiation and proliferation. The results from our research will clarify the underlying mechanism of PSORI-CM02 on psoriasis, finding a novel treatment strategy for traditional Chinese medicine in the treatment of psoriasis.

银屑病是T细胞介导的免疫性疾病，影响全球2-3%的人口。银屑灵优化方是国医大师禤国维治疗银屑病的经验方，临床疗效确切，作用机制亟需阐明。Treg是一种具有免疫调节功能的T细胞亚群，抑制PI3K/AKT/mTOR信号通路能够诱导Foxp3的表达，上调Treg比例，在银屑病发生和治疗中起到重要作用。课题组研究发现，银屑灵优化方能够有效降低银屑病小鼠皮损，抑制p-mTOR和p-AKT表达，上调CD4+Foxp3+Treg比例，因此，提出“银屑灵优化方通过抑制PI3K/AKT/mTOR信号通路上调CD4+Foxp3+Treg治疗银屑病”的科学假说。本项目通过分选银屑病患者和银屑病小鼠Naïe CD4+T细胞以及Treg，研究该方对PI3K/AKT/mTOR信号通路和Treg细胞分化增殖的作用机制。本课题将阐明银屑灵优化方治疗银屑病的作用机制，为中药复方治疗银屑病机理研究提供新的靶点。

银屑病是T细胞介导的免疫性疾病，影响2-3%的人口。银屑灵优化方是国医大师禤国维治疗银屑病的验方，临床疗效确切，作用机制亟需阐明。前期研究发现，银屑灵优化方能够有效缓解银屑病小鼠皮损情况，抑制p-mTOR和p-AKT表达，上调CD4+Foxp3+Treg细胞比例，因此，提出“银屑灵优化方通过抑制PI3K/AKT/mTOR信号通路上调CD4+Foxp3+Treg治疗银屑病”的科学假说。研究发现，银屑灵优化方能够有效改善咪喹莫特诱导银屑病小鼠模型，抑制PI3K/AKT/mTOR信号通路，上调脾脏和淋巴结CD4+Foxp3+Treg细胞比例，同时促进角质细胞自噬。银屑灵优化方还能抑制HaCaT细胞增殖，可能与抑制PI3K/AKT/mTOR信号通路促进其自噬相关，此外还能促使Treg细胞的增殖和分化。有效单体甘草次酸能够通过通过抑制mTOR和STAT3信号通路，上调脾脏和淋巴结CD4+Foxp3+Treg细胞比例，对银屑病模型有治疗作用。研究初步阐明银屑灵优化方治疗银屑病的作用机制，可为中药复方治疗银屑病机理研究提供新的靶点。