ALA光动力通过募集天然淋巴样细胞重建皮脂腺稳态治疗痤疮的机制研究

ALA光动力治疗重度痤疮安全有效，但机制尚未完全阐明。新近研究发现皮脂腺稳态失衡是痤疮的重要致病因素，稳态失衡的关键在于皮脂腺周围天然淋巴样细胞（ILCs）的缺失。本课题组前期研究ALA光动力治疗前、后重度痤疮临床样本的基因表达谱芯片时，意外发现治疗后多个ILCs相关标志物表达均显著上调，进一步通过动物实验确证光动力治疗后皮脂腺周围ILCs明显增多，结合最新研究提出科学假说：ALA光动力可能通过上调炎症因子募集ILCs，分泌TNFα/LTα，抑制皮脂腺细胞Notch信号通路，重建皮脂腺稳态，发挥痤疮治疗作用。本课题拟进一步应用临床样本、金黄地鼠痤疮模型及课题组前期自主构建的中国人永生化皮脂腺细胞系，从体内、细胞及分子水平探索ALA光动力治疗后ILCs的募集机制及其重建皮脂腺稳态的关键信号通路。本课题的完成有助于完善ALA光动力治疗痤疮的机制理论，为优化ALA光动力的临床应用提供新策略。

ALA photodynamic therapy（ALA-PDT）is safe and effective for severe acne, but the mechanism has not been fully elucidated. Recent studies have found that the imbalance of sebaceous gland(SG) homeostasis is an important pathogenic factor for acne. The key role of SG homeostasis imbalance is the loss of innate lymphoid cells (ILCs) around sebaceous glands. When analyzing the gene expression profile of clinical samples of severe acne before and after ALA-PDT in the previous research of our group, it was unexpectedly found that the expression of multiple ILCs-related markers were significantly up-regulated after treatment，and further animal experiments confirmed the ILCs increased significantly around sebaceous glands after ALA-PDT. Combined with the latest studies, a scientific hypothesis was put forward: ALA-PDT recruits ILCs by up-regulating inflammatory factors, secretes TNFα/LTα, inhibits the Notch signaling pathway of sebaceous gland cells, reconstructs SG homeostasis, and plays a role in acne treatment. This project intends to further use clinical samples, golden hamster acne model and the Chinese immortalized sebaceous gland cell line independently constructed by our own research group in the early stage to explore the recruitment mechanism of ILCs and the key signal pathway of SG homeostasis reconstruction after ALA-PDT at the in vivo, cellular and molecular levels. The completion of this topic will help improve the mechanism theory of ALA-PDT for acne, and provide a new strategy for optimizing the clinical application of ALA-PDT.