Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study
Sepsis is a leading cause of morbidity and mortality in the intensive care unit, which is caused by unregulated inflammatory response leading to organ injuries. Ulinastatin (UTI), an immunomodulatory agent, is widely used in clinical practice and is associated with improved outcomes in sepsis. But i...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.882774/full |
| _version_ | 1811307660286361600 |
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| author | Lin Chen Senjun Jin Min Yang Chunmei Gui Yingpu Yuan Guangtao Dong Weizhong Zeng Jing Zeng Guoxin Hu Lujun Qiao Jinhua Wang Yonglin Xi Jian Sun Nan Wang Minmin Wang Lifeng Xing Yi Yang Yan Teng Junxia Hou Qiaojie Bi Huabo Cai Gensheng Zhang Yucai Hong Zhongheng Zhang |
| author_facet | Lin Chen Senjun Jin Min Yang Chunmei Gui Yingpu Yuan Guangtao Dong Weizhong Zeng Jing Zeng Guoxin Hu Lujun Qiao Jinhua Wang Yonglin Xi Jian Sun Nan Wang Minmin Wang Lifeng Xing Yi Yang Yan Teng Junxia Hou Qiaojie Bi Huabo Cai Gensheng Zhang Yucai Hong Zhongheng Zhang |
| author_sort | Lin Chen |
| collection | DOAJ |
| description | Sepsis is a leading cause of morbidity and mortality in the intensive care unit, which is caused by unregulated inflammatory response leading to organ injuries. Ulinastatin (UTI), an immunomodulatory agent, is widely used in clinical practice and is associated with improved outcomes in sepsis. But its underlying mechanisms are largely unknown. Our study integrated bulk and single cell RNA-seq data to systematically explore the potential mechanisms of the effects of UTI in sepsis. After adjusting for potential confounders in the negative binomial regression model, there were more genes being downregulated than being upregulated in the UTI group. These down-regulated genes were enriched in the neutrophil involved immunity such as neutrophil activation and degranulation, indicating the immunomodulatory effects of UTI is mediated via regulation of neutrophil activity. By deconvoluting the bulk RNA-seq samples to obtain fractions of cell types, the Myeloid-derived suppressor cells (MDSC) were significantly expanded in the UTI treated samples. Further cell-cell communication analysis revealed some signaling pathways such as ANEEXIN, GRN and RESISTIN that might be involved in the immunomodulatory effects of UTI. The study provides a comprehensive reference map of transcriptional states of sepsis treated with UTI, as well as a general framework for studying UTI-related mechanisms. |
| first_indexed | 2024-04-13T09:08:19Z |
| format | Article |
| id | doaj.art-b05f1ff99f2e42f9b0ebf7b4b5c4780d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T09:08:19Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b05f1ff99f2e42f9b0ebf7b4b5c4780d2022-12-22T02:52:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.882774882774Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort StudyLin Chen0Senjun Jin1Min Yang2Chunmei Gui3Yingpu Yuan4Guangtao Dong5Weizhong Zeng6Jing Zeng7Guoxin Hu8Lujun Qiao9Jinhua Wang10Yonglin Xi11Jian Sun12Nan Wang13Minmin Wang14Lifeng Xing15Yi Yang16Yan Teng17Junxia Hou18Qiaojie Bi19Huabo Cai20Gensheng Zhang21Yucai Hong22Zhongheng Zhang23Department of Critical Care Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, ChinaDepartment of Emergency, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaThe 2nd Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Critical Care Medicine, The First People’s Hospital of Changde City, Changde, ChinaDepartment of Critical Care Medicine, The First People’s Hospital of Changde City, Changde, ChinaDepartment of Emergency Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, ChinaDepartment of Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, ChinaEmergency Department, Shengli Oilfield Central Hospital, Dongying, ChinaEmergency Department, Shengli Oilfield Central Hospital, Dongying, ChinaDepartment of Critical Care Medicine, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, ChinaDepartment of Critical Care Medicine, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, ChinaDepartment of Critical Care Medicine, Lishui Center Hospital, Lishui, China0Department of Critical Care Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China0Department of Critical Care Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China1Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China2Department of Emergency Medicine, The Second Hospital of Jiaxing, Jiaxing, China3Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China3Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China4Department of Emergency, Qingdao Municipal Hospital, QingDao University School of Medicine, Qingdao, China1Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China5Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China6Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China6Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaSepsis is a leading cause of morbidity and mortality in the intensive care unit, which is caused by unregulated inflammatory response leading to organ injuries. Ulinastatin (UTI), an immunomodulatory agent, is widely used in clinical practice and is associated with improved outcomes in sepsis. But its underlying mechanisms are largely unknown. Our study integrated bulk and single cell RNA-seq data to systematically explore the potential mechanisms of the effects of UTI in sepsis. After adjusting for potential confounders in the negative binomial regression model, there were more genes being downregulated than being upregulated in the UTI group. These down-regulated genes were enriched in the neutrophil involved immunity such as neutrophil activation and degranulation, indicating the immunomodulatory effects of UTI is mediated via regulation of neutrophil activity. By deconvoluting the bulk RNA-seq samples to obtain fractions of cell types, the Myeloid-derived suppressor cells (MDSC) were significantly expanded in the UTI treated samples. Further cell-cell communication analysis revealed some signaling pathways such as ANEEXIN, GRN and RESISTIN that might be involved in the immunomodulatory effects of UTI. The study provides a comprehensive reference map of transcriptional states of sepsis treated with UTI, as well as a general framework for studying UTI-related mechanisms.https://www.frontiersin.org/articles/10.3389/fimmu.2022.882774/fullsepsissingle cellulinastatinRNA-seqimmunosuppression |
| spellingShingle | Lin Chen Senjun Jin Min Yang Chunmei Gui Yingpu Yuan Guangtao Dong Weizhong Zeng Jing Zeng Guoxin Hu Lujun Qiao Jinhua Wang Yonglin Xi Jian Sun Nan Wang Minmin Wang Lifeng Xing Yi Yang Yan Teng Junxia Hou Qiaojie Bi Huabo Cai Gensheng Zhang Yucai Hong Zhongheng Zhang Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study Frontiers in Immunology sepsis single cell ulinastatin RNA-seq immunosuppression |
| title | Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study |
| title_full | Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study |
| title_fullStr | Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study |
| title_full_unstemmed | Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study |
| title_short | Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study |
| title_sort | integrated single cell and bulk rna seq analysis revealed immunomodulatory effects of ulinastatin in sepsis a multicenter cohort study |
| topic | sepsis single cell ulinastatin RNA-seq immunosuppression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.882774/full |
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