Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Key Laboratary of Aging Biology, Xiangya Hospital, Central South University, Changsha, China.
PeerJ. 2023 Sep 26;11:e15976. doi: 10.7717/peerj.15976. eCollection 2023.
Rosacea is a chronic inflammatory skin disease originated from damaged skin barrier and innate/adaptive immune dysregulation. Toll-like receptors (TLRs) sense injured skin and initiate downstream inflammatory and immune responses, whose role in rosacea is not fully understood. Here, via RNA-sequencing analysis, we found that the TLR signaling pathway is the top-ranked signaling pathway enriched in rosacea skin lesions, in which TLR7 is highlighted and positively correlated with the inflammation severity of disease. In LL37-induced rosacea-like mouse models, silencing TLR7 prevented the development of rosacea-like skin inflammation. Specifically, we demonstrated that overexpressing TLR7 in keratinocytes stimulates rapamycin-sensitive mTOR complex 1 (mTORC1) pathway NFκB signaling. Ultimately, TLR7/NFκ B/mTORC1 axis promotes the production of cytokines and chemokines, leading to the migration of CD4T cells, which are infiltrated in the lesional skin of rosacea. Our report reveals the crucial role of TLR7 in rosacea pathogenesis and indicatesa promising candidate for rosacea treatments.
酒渣鼻是一种源于皮肤屏障损伤和固有/适应性免疫失调的慢性炎症性皮肤疾病。Toll 样受体（TLR）感知受损皮肤并启动下游炎症和免疫反应，但其在酒渣鼻中的作用尚未完全阐明。在这里，通过 RNA 测序分析，我们发现 TLR 信号通路是在酒渣鼻皮损中富集的排名最高的信号通路，其中 TLR7 最为突出，并与疾病炎症严重程度呈正相关。在 LL37 诱导的酒渣鼻样小鼠模型中，沉默 TLR7 可预防酒渣鼻样皮肤炎症的发生。具体而言，我们证明了角质形成细胞中 TLR7 的过表达可刺激雷帕霉素敏感的 mTOR 复合物 1（mTORC1）途径 NFκB 信号。最终，TLR7/NFκB/mTORC1 轴促进细胞因子和趋化因子的产生，导致浸润在酒渣鼻皮损中的 CD4T 细胞迁移。我们的报告揭示了 TLR7 在酒渣鼻发病机制中的关键作用，并为酒渣鼻治疗提供了一个有前途的候选靶点。
