Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice

Autor: Runping Duan, Tianfu Wang, Zhaohuai Li, Loujing Jiang, Xiaoyang Yu, Daquan He, Tianyu Tao, Xiuxing Liu, Zhaohao Huang, Lei Feng, Wenru Su
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 21, Iss 1, Pp 1-17 (2024)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-024-03308-z
Popis: Abstract Background 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. Methods 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. Results 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. Conclusions The KD induces inhibitory structural and functional alterations in immune cells from lymph nodes to retina, suggesting its potential as a therapy for uveitis.
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