Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses
Background: Type I interferon signature is one of the most important features of systemic lupus erythematosus (SLE), which indicates an active immune response to antigen invasion. Characteristics of type I interferon-stimulated genes (ISGs) in SLE patients have not been well described thus far. Meth...
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| Language: | English |
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Elsevier
2021-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642100270X |
| _version_ | 1818891333279940608 |
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| author | Yiyao Deng Ying Zheng Delun Li Quan Hong Min Zhang Qinggang Li Bo Fu Lingling Wu Xu Wang Wanjun Shen Yingjie Zhang Jiakai Chang Kangkang Song Xiaomin Liu Shunlai Shang Guangyan Cai Xiangmei Chen |
| author_facet | Yiyao Deng Ying Zheng Delun Li Quan Hong Min Zhang Qinggang Li Bo Fu Lingling Wu Xu Wang Wanjun Shen Yingjie Zhang Jiakai Chang Kangkang Song Xiaomin Liu Shunlai Shang Guangyan Cai Xiangmei Chen |
| author_sort | Yiyao Deng |
| collection | DOAJ |
| description | Background: Type I interferon signature is one of the most important features of systemic lupus erythematosus (SLE), which indicates an active immune response to antigen invasion. Characteristics of type I interferon-stimulated genes (ISGs) in SLE patients have not been well described thus far. Methods: We analyzed 35,842 cells of PBMC single-cell RNA sequencing data of five SLE patients and three healthy controls. Thereafter, 178 type I ISGs among DEGs of all cell clusters were screened based on the Interferome Database and AUCell package was used for ISGs activity calculation. To determine whether common ISG features exist in PBMCs and kidneys of patients with SLE, we analyzed kidney transcriptomic data from patients with lupus nephritis (LN) from the GEO database. MRL/lpr mice model were used to verify our findings. Findings: We found that monocytes, B cells, dendritic cells, and granulocytes were significantly increased in SLE patients, while subsets of T cells were significantly decreased. Neutrophils and low-density granulocytes (LDGs) exhibited the highest ISG activity. GO and pathway enrichment analyses showed that DEGs focused on leukocyte activation, cell secretion, and pathogen infection. Thirty-one common ISGs were found expressed in both PBMCs and kidneys; these ISGs were also most active in neutrophils and LDGs. Transcription factors including PLSCR1, TCF4, IRF9 and STAT1 were found to be associated to ISGs expression. Consistently, we found granulocyte infiltration in the kidneys of MRL/lpr mice. Granulocyte inhibitor Avacopan reduced granulocyte infiltration and reversed renal conditions in MRL/lpr mice. Interpretation: This study shows for the first time, the use of the AUCell method to describe ISG activity of granulocytes in SLE patients. Moreover, Avacopan may serve as a granulocyte inhibitor for treatment of lupus patients in the future. |
| first_indexed | 2024-12-19T17:39:08Z |
| format | Article |
| id | doaj.art-f35b5b421aa040f895b29a00072df238 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-19T17:39:08Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-f35b5b421aa040f895b29a00072df2382022-12-21T20:12:16ZengElsevierEBioMedicine2352-39642021-08-0170103477Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analysesYiyao Deng0Ying Zheng1Delun Li2Quan Hong3Min Zhang4Qinggang Li5Bo Fu6Lingling Wu7Xu Wang8Wanjun Shen9Yingjie Zhang10Jiakai Chang11Kangkang Song12Xiaomin Liu13Shunlai Shang14Guangyan Cai15Xiangmei Chen16Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, China; School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou 510080, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, China; School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou 510080, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, China; School of Medicine, Nankai University, Tianjin 300071, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, ChinaDepartment of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, China; Corresponding author.Background: Type I interferon signature is one of the most important features of systemic lupus erythematosus (SLE), which indicates an active immune response to antigen invasion. Characteristics of type I interferon-stimulated genes (ISGs) in SLE patients have not been well described thus far. Methods: We analyzed 35,842 cells of PBMC single-cell RNA sequencing data of five SLE patients and three healthy controls. Thereafter, 178 type I ISGs among DEGs of all cell clusters were screened based on the Interferome Database and AUCell package was used for ISGs activity calculation. To determine whether common ISG features exist in PBMCs and kidneys of patients with SLE, we analyzed kidney transcriptomic data from patients with lupus nephritis (LN) from the GEO database. MRL/lpr mice model were used to verify our findings. Findings: We found that monocytes, B cells, dendritic cells, and granulocytes were significantly increased in SLE patients, while subsets of T cells were significantly decreased. Neutrophils and low-density granulocytes (LDGs) exhibited the highest ISG activity. GO and pathway enrichment analyses showed that DEGs focused on leukocyte activation, cell secretion, and pathogen infection. Thirty-one common ISGs were found expressed in both PBMCs and kidneys; these ISGs were also most active in neutrophils and LDGs. Transcription factors including PLSCR1, TCF4, IRF9 and STAT1 were found to be associated to ISGs expression. Consistently, we found granulocyte infiltration in the kidneys of MRL/lpr mice. Granulocyte inhibitor Avacopan reduced granulocyte infiltration and reversed renal conditions in MRL/lpr mice. Interpretation: This study shows for the first time, the use of the AUCell method to describe ISG activity of granulocytes in SLE patients. Moreover, Avacopan may serve as a granulocyte inhibitor for treatment of lupus patients in the future.http://www.sciencedirect.com/science/article/pii/S235239642100270XSingle-cell RNA sequencingInterferonGranulocytesSystemic lupus erythematosusLupus nephritis |
| spellingShingle | Yiyao Deng Ying Zheng Delun Li Quan Hong Min Zhang Qinggang Li Bo Fu Lingling Wu Xu Wang Wanjun Shen Yingjie Zhang Jiakai Chang Kangkang Song Xiaomin Liu Shunlai Shang Guangyan Cai Xiangmei Chen Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses EBioMedicine Single-cell RNA sequencing Interferon Granulocytes Systemic lupus erythematosus Lupus nephritis |
| title | Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses |
| title_full | Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses |
| title_fullStr | Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses |
| title_full_unstemmed | Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses |
| title_short | Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses |
| title_sort | expression characteristics of interferon stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses |
| topic | Single-cell RNA sequencing Interferon Granulocytes Systemic lupus erythematosus Lupus nephritis |
| url | http://www.sciencedirect.com/science/article/pii/S235239642100270X |
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