Frontiers in Immunology (May 2023)
CD16+ monocytes are involved in the hyper-inflammatory state of Prader-Willi Syndrome by single-cell transcriptomic analysis
- Yunyun Xu,
- Yunyun Xu,
- Yunyun Xu,
- Yunyun Xu,
- Yunyun Xu,
- Xu Hou,
- Xu Hou,
- Honglin Guo,
- Honglin Guo,
- Honglin Guo,
- Zhenyu Yao,
- Zhenyu Yao,
- Zhenyu Yao,
- Zhenyu Yao,
- Xiude Fan,
- Xiude Fan,
- Xiude Fan,
- Xiude Fan,
- Chao Xu,
- Chao Xu,
- Chao Xu,
- Chao Xu,
- Guimei Li,
- Yanzhou Wang,
- Yan Sun,
- Ling Gao,
- Ling Gao,
- Yongfeng Song,
- Yongfeng Song,
- Yongfeng Song,
- Yongfeng Song,
- Yongfeng Song,
- Jiajun Zhao,
- Jiajun Zhao,
- Jiajun Zhao,
- Jiajun Zhao,
- Jiajun Zhao,
- Jiajun Zhao
Affiliations
- Yunyun Xu
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Yunyun Xu
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Yunyun Xu
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Yunyun Xu
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Yunyun Xu
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Xu Hou
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Xu Hou
- Stem Cell Research Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Honglin Guo
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Honglin Guo
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Honglin Guo
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Zhenyu Yao
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Zhenyu Yao
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Zhenyu Yao
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Zhenyu Yao
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Xiude Fan
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Xiude Fan
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Xiude Fan
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Xiude Fan
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Chao Xu
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Chao Xu
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Chao Xu
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Chao Xu
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Guimei Li
- Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Yanzhou Wang
- Department of Pediatric Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Yan Sun
- Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Ling Gao
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Ling Gao
- Scientific Research Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Yongfeng Song
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Yongfeng Song
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Yongfeng Song
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Yongfeng Song
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Yongfeng Song
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, China
- Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Jiajun Zhao
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China
- Jiajun Zhao
- Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China
- Jiajun Zhao
- Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China
- Jiajun Zhao
- Stem Cell Research Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- DOI
- https://doi.org/10.3389/fimmu.2023.1153730
- Journal volume & issue
-
Vol. 14
Abstract
BackgroundPatients with Prader-Willi syndrome (PWS) have a reduced life expectancy due to inflammation-related disease including cardiovascular disease and diabetes. Abnormal activation of peripheral immune system is postulated as a contributor. However, detailed features of the peripheral immune cells in PWS have not been fully elucidated.MethodsSerum inflammatory cytokines were measured in healthy controls (n=13) and PWS patients (n=10) using a 65- multiplex cytokine assays. Changes of the peripheral immune cells in PWS was assessed by single-cell RNA sequencing (scRNA-seq) and high-dimensional mass cytometry (CyTOF) using peripheral blood mononuclear cells (PBMCs) from PWS patients (n=6) and healthy controls (n=12).ResultsPWS patients exhibited hyper-inflammatory signatures in PBMCs and monocytes were the most pronounced. Most inflammatory serum cytokines were increased in PWS, including IL-1β, IL-2R, IL-12p70, and TNF-α. The characteristics of monocytes evaluated by scRNA-seq and CyTOF showed that CD16+ monocytes were significantly increased in PWS patients. Functional pathway analysis revealed that CD16+ monocytes upregulated pathways in PWS were closely associated with TNF/IL-1β- driven inflammation signaling. The CellChat analysis identified CD16+ monocytes transmitted chemokine and cytokine signaling to drive inflammatory process in other cell types. Finally, we explored the PWS deletion region 15q11–q13 might be responsible for elevated levels of inflammation in the peripheral immune system.ConclusionThe study highlights that CD16+ monocytes contributor to the hyper-inflammatory state of PWS which provides potential targets for immunotherapy in the future and expands our knowledge of peripheral immune cells in PWS at the single cell level for the first time.
Keywords
