Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice
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 Util...
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BMC
2024-12-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-024-03308-z |
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| author | Runping Duan Tianfu Wang Zhaohuai Li Loujing Jiang Xiaoyang Yu Daquan He Tianyu Tao Xiuxing Liu Zhaohao Huang Lei Feng Wenru Su |
| author_facet | Runping Duan Tianfu Wang Zhaohuai Li Loujing Jiang Xiaoyang Yu Daquan He Tianyu Tao Xiuxing Liu Zhaohao Huang Lei Feng Wenru Su |
| author_sort | Runping Duan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dbfc9480e05d4c85b4facf1304a10ec8 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-dbfc9480e05d4c85b4facf1304a10ec82024-12-08T12:38:34ZengBMCJournal of Neuroinflammation1742-20942024-12-0121111710.1186/s12974-024-03308-zKetogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in miceRunping Duan0Tianfu Wang1Zhaohuai Li2Loujing Jiang3Xiaoyang Yu4Daquan He5Tianyu Tao6Xiuxing Liu7Zhaohao Huang8Lei Feng9Wenru Su10State 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 DiseasesState 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 DiseasesState 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 DiseasesState 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 DiseasesGuangzhou University of Chinese MedicineState 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 DiseasesState 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 DiseasesState 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 DiseasesState 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 DiseasesEye Center, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract 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.https://doi.org/10.1186/s12974-024-03308-zKetogenic diet (KD)Immune microenvironmentUveitisExperimental autoimmune uveitis (EAU) |
| spellingShingle | Runping Duan Tianfu Wang Zhaohuai Li Loujing Jiang Xiaoyang Yu Daquan He Tianyu Tao Xiuxing Liu Zhaohao Huang Lei Feng Wenru Su Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice Journal of Neuroinflammation Ketogenic diet (KD) Immune microenvironment Uveitis Experimental autoimmune uveitis (EAU) |
| title | Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice |
| title_full | Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice |
| title_fullStr | Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice |
| title_full_unstemmed | Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice |
| title_short | Ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice |
| title_sort | ketogenic diet modulates immune cell transcriptional landscape and ameliorates experimental autoimmune uveitis in mice |
| topic | Ketogenic diet (KD) Immune microenvironment Uveitis Experimental autoimmune uveitis (EAU) |
| url | https://doi.org/10.1186/s12974-024-03308-z |
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