Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease
Glucocorticoids (GCs) are widely used immunosuppressive drugs for autoimmune diseases, although considerable gaps exist between current knowledge of the mechanisms of GCs and their conclusive immune-regulatory effects. Here we generated a single-cell transcriptional immune cell atlas based on predni...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.739605/full |
| _version_ | 1818455982466924544 |
|---|---|
| author | He Li Yuehan Gao Lihui Xie Rong Wang Runping Duan Zhaohuai Li Binyao Chen Lei Zhu Xianggui Wang Xianggui Wang Wenru Su |
| author_facet | He Li Yuehan Gao Lihui Xie Rong Wang Runping Duan Zhaohuai Li Binyao Chen Lei Zhu Xianggui Wang Xianggui Wang Wenru Su |
| author_sort | He Li |
| collection | DOAJ |
| description | Glucocorticoids (GCs) are widely used immunosuppressive drugs for autoimmune diseases, although considerable gaps exist between current knowledge of the mechanisms of GCs and their conclusive immune-regulatory effects. Here we generated a single-cell transcriptional immune cell atlas based on prednisone-treated or untreated experimental autoimmune uveitis (EAU) mice. Immune cells were globally activated in EAU, and prednisone partially reversed this effect in terms of cell composition, gene expression, transcription factor regulation, and cell-cell communication. Prednisone exerted considerable rescue effects on T and B cells and increased the proportion of neutrophils. Besides commonly regulated transcriptional factors (Fosb, Jun, Jund), several genes were only regulated in certain cell types (e.g. Cxcr4 and Bhlhe40 in T cells), suggesting cell-type-dependent immunosuppressive properties of GC. These findings provide new insights into the mechanisms behind the properties and cell-specific effects of GCs and can potentially benefit immunoregulatory therapy development. |
| first_indexed | 2024-12-14T22:19:25Z |
| format | Article |
| id | doaj.art-04162b452db64c7789e691775f0d74e1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T22:19:25Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-04162b452db64c7789e691775f0d74e12022-12-21T22:45:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.739605739605Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune DiseaseHe Li0Yuehan Gao1Lihui Xie2Rong Wang3Runping Duan4Zhaohuai Li5Binyao Chen6Lei Zhu7Xianggui Wang8Xianggui Wang9Wenru Su10State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaEye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaGlucocorticoids (GCs) are widely used immunosuppressive drugs for autoimmune diseases, although considerable gaps exist between current knowledge of the mechanisms of GCs and their conclusive immune-regulatory effects. Here we generated a single-cell transcriptional immune cell atlas based on prednisone-treated or untreated experimental autoimmune uveitis (EAU) mice. Immune cells were globally activated in EAU, and prednisone partially reversed this effect in terms of cell composition, gene expression, transcription factor regulation, and cell-cell communication. Prednisone exerted considerable rescue effects on T and B cells and increased the proportion of neutrophils. Besides commonly regulated transcriptional factors (Fosb, Jun, Jund), several genes were only regulated in certain cell types (e.g. Cxcr4 and Bhlhe40 in T cells), suggesting cell-type-dependent immunosuppressive properties of GC. These findings provide new insights into the mechanisms behind the properties and cell-specific effects of GCs and can potentially benefit immunoregulatory therapy development.https://www.frontiersin.org/articles/10.3389/fimmu.2021.739605/fullprednisoneglucocorticoidsautoimmune uveitissingle-cell RNA sequencingCNS autoimmune diseases |
| spellingShingle | He Li Yuehan Gao Lihui Xie Rong Wang Runping Duan Zhaohuai Li Binyao Chen Lei Zhu Xianggui Wang Xianggui Wang Wenru Su Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease Frontiers in Immunology prednisone glucocorticoids autoimmune uveitis single-cell RNA sequencing CNS autoimmune diseases |
| title | Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease |
| title_full | Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease |
| title_fullStr | Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease |
| title_full_unstemmed | Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease |
| title_short | Prednisone Reprograms the Transcriptional Immune Cell Landscape in CNS Autoimmune Disease |
| title_sort | prednisone reprograms the transcriptional immune cell landscape in cns autoimmune disease |
| topic | prednisone glucocorticoids autoimmune uveitis single-cell RNA sequencing CNS autoimmune diseases |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.739605/full |
| work_keys_str_mv | AT heli prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT yuehangao prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT lihuixie prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT rongwang prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT runpingduan prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT zhaohuaili prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT binyaochen prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT leizhu prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT xiangguiwang prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT xiangguiwang prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease AT wenrusu prednisonereprogramsthetranscriptionalimmunecelllandscapeincnsautoimmunedisease |