Febrile temperature-regulated TRPV1 in CD4+ T cells mediates neuroinflammation in complex febrile seizures

作者：Shuo Kong, Xianglei Jia, Xin Liang, Yu Chen, Jingyi Liang, Yan Zhang, Na‐Qiong Wu, Song Su, Tao-Xiang Chen, Xiaohua He, Jun Yin, Song Han, Wanhong Liu, Yuanteng Fan, Jianming Xu, Biwen Peng · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03421-7 · 被引用次数：10 · 研究领域：Ion Channels and Receptors、Epilepsy research and treatment、Vagus Nerve Stimulation Research

BACKGROUND: Febrile seizures (FS) are the most prevalent convulsive disorder in children characterized by a high recurrence rate. However, the interaction between adaptive and innate immunity in the recurrence of FS remains poorly understood, and the molecular pathways involved are unclear. The objective of this study is to elucidate the role of Th17 cells in seizure susceptibility following complex febrile seizures (CFS), and to explore the regulatory mechanisms underlying Th17 cell differentiation and function under hyperthermic conditions through transient receptor potential vanilloid 1 (TRPV1). METHODS: RNA sequencing was employed to validate the seizure susceptibility following CFS and to explore the potential mechanisms by which high temperature contributes to Th17 cell differentiation. Neuronal excitability and damage were examined using Multi-electrode array (MEA) analysis and Nissl staining. Flow cytometry, chromatin immunoprecipitation (ChIP) analysis, and immunofluorescence (IF) were applied to examine how TRPV1 facilitates Th17 cell differentiation. RESULTS: Our study demonstrates that proinflammatory Th17 cells exhibit enhanced differentiation in a CFS mouse model and exacerbate blood-brain barrier (BBB) disruption. After infiltrating the central nervous system (CNS), Th17 cells promote neuroinflammation by activating microglia via IL-17A. Mechanistically, TRPV1 is critical for Th17 cell differentiation and function. Activated by febrile temperature both in vivo ...