Duan Runping, Wang Tianfu, Li Zhaohuai, Jiang Loujing, Yu Xiaoyang, He Daquan, Tao Tianyu, Liu Xiuxing, Huang Zhaohao, Feng Lei, Su Wenru
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China.
Guangzhou University of Chinese Medicine, Guangzhou, 510060, China.
J Neuroinflammation. 2024 Dec 3;21(1):319. doi: 10.1186/s12974-024-03308-z.
Uveitis manifests as immune-mediated inflammatory disorders within the eye, posing a serious threat to vision. The ketogenic diet (KD) has emerged as a promising dietary intervention, yet its impact on the immune microenvironments and role in uveitis remains unclear.
Utilizing single-cell RNA sequencing (scRNA-seq) data from lymph node and retina of mice, we conduct a comprehensive investigation into the effects of KD on immune microenvironments. Flow cytometry is conducted to verify the potential mechanisms.
This study demonstrates that KD alters the composition and function of immune profiles. Specifically, KD promotes the differentiation of Treg cells and elevates its proportion in heathy mice. In response to experimental autoimmune uveitis challenges, KD alleviates the inflammatory symptoms, lowers CD4 T cell pathogenicity, and corrects the Th17/Treg imbalance. Additionally, KD decreases the proportion of Th17 cell and increases Treg cells in the retina. Analysis of combined retinal and CDLN immune cells reveals that retinal immune cells, particularly CD4 T cells, exhibit heightened inflammatory responses, which KD partially reverses.
The KD induces inhibitory structural and functional alterations in immune cells from lymph nodes to retina, suggesting its potential as a therapy for uveitis.
葡萄膜炎表现为眼内免疫介导的炎症性疾病，对视力构成严重威胁。生酮饮食（KD）已成为一种有前景的饮食干预方式，但其对免疫微环境的影响以及在葡萄膜炎中的作用仍不清楚。
利用小鼠淋巴结和视网膜的单细胞RNA测序（scRNA-seq）数据，我们全面研究了KD对免疫微环境的影响。进行流式细胞术以验证潜在机制。
本研究表明，KD改变了免疫图谱的组成和功能。具体而言，KD促进了调节性T细胞（Treg）的分化，并提高了其在健康小鼠中的比例。在应对实验性自身免疫性葡萄膜炎挑战时，KD减轻了炎症症状，降低了CD4 T细胞的致病性，并纠正了辅助性T细胞17（Th17）/调节性T细胞的失衡。此外，KD降低了视网膜中Th17细胞的比例并增加了调节性T细胞。对视网膜和颈深淋巴结（CDLN）联合免疫细胞的分析表明，视网膜免疫细胞，特别是CD4 T细胞，表现出增强的炎症反应，而KD可部分逆转这种反应。
KD在从淋巴结到视网膜的免疫细胞中诱导了抑制性结构和功能改变，表明其作为葡萄膜炎治疗方法的潜力。
